bluuebunny/crossref_metadata_2025 huggingface dataset:
Mouse PDX Trial Suggests Synergy of Concurrent Inhibition of RAF and EGFR in Colorectal Cancer with BRAF or KRAS Mutations
Authors: Yao Yung-mae M. , Donoho Gregory P. , Iversen Philip W. , Zhang Youyan , Van Horn Robert D. , Forest Amelie , Novosiadly Ruslan D. , Webster Yue Wang , Ebert Philip , Bray Steven , Ting Jason C. , Aggarwal Amit , Henry James R. , Tiu Ramon V. , Plowman Gregory D. , Peng Sheng-Bin
Published: June 2017

Purpose: To evaluate the antitumor efficacy of cetuximab in combination with LSN3074753, an analog of LY3009120 and pan-RAF inhibitor in 79 colorectal cancer patient-derived xenograft (PDX) models.

Experimental Design: Seventy-nine well-characterized colorectal cancer PDX models were employed to conduct a single mouse per treatment group (n = 1) trial.

Results: Consistent with clinical results, cetuximab was efficacious in wild-type KRAS and BRAF PDX models, with an overall response rate of 6.3% and disease control rate (DCR) of 20.3%. LSN3074753 was active in a small subset of PDX models that harbored KRAS or BRAF mutations. However, the combination treatment displayed the enhanced antitumor activity with DCR of 35.4%. Statistical analysis revealed that BRAF and KRAS mutations were the best predictors of the combinatorial activity and were significantly associated with synergistic effect with a P value of 0.01 compared with cetuximab alone. In 12 models with BRAF mutations, the combination therapy resulted in a DCR of 41.7%, whereas either monotherapy had a DCR of 8.3%. Among 44 KRAS mutation models, cetuximab or LSN3074753 monotherapy resulted in a DCR of 13.6% or 11.4%, respectively, and the combination therapy increased DCR to 34.1%. Molecular analysis suggests that EGFR activation is a potential feedback and resistant mechanism of pan-RAF inhibition.

Conclusions: MAPK and EGFR pathway activations are two major molecular hallmarks of colorectal cancer. This mouse PDX trial recapitulated clinical results of cetuximab. Concurrent EGFR and RAF inhibition demonstrated synergistic antitumor activity for colorectal cancer PDX models with a KRAS or BRAF mutation. Clin Cancer Res; 23(18); 5547–60. ©2017 AACR.
Role of Platelet-Derived Tgfβ1 in the Progression of Ovarian Cancer
Authors: Hu Qianghua , Hisamatsu Takeshi , Haemmerle Monika , Cho Min Soon , Pradeep Sunila , Rupaimoole Rajesha , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel , Wong Stephen T.C. , Sood Anil K. , Afshar-Kharghan Vahid
Published: June 2017

Purpose: Transforming growth factor β1 (Tgfβ1) plays an important role in cancer. Most of Tgfβ1 in plasma is from platelets; thus, we studied whether platelet Tgfβ1 has any role in the progression of ovarian cancer, and whether this role is limited to metastasis or also involves the growth of primary tumors.

Experimental Design: We compared the growth of murine ovarian cancer cell-induced tumors in platelet-specific Tgfβ1-deficient mice and wild-type mice. Using resected tumor nodules, we studied the effect of platelet Tgfβ1 on neoangiogenesis and on platelet extravasation into tumors. To investigate the effect of Tgfβ1 at different stages of ovarian cancer, we reduced expression of Tgfβ1 receptor (its TgfβR1 component) in tumors at different time points after injection of cancer cells, and compared the final tumor size.

Results: Lack of platelet Tgfβ1 in mice reduced tumor growth, neoangiogenesis, and platelet extravasation. Ovarian cancer tumors in platelet-specific Tgfβ1-deficient mice reached less than half of their size in wild-type littermates. Knockdown of TgfβR1 on cancer cells in the first 2 weeks after their injection reduced tumor growth, but was less effective if initiated after 3 weeks.

Conclusions: We showed that platelet Tgfβ1 increased the growth of primary tumors in murine models of ovarian cancer. We also showed that inhibition of TgfβR1 is more effective in reducing the growth of ovarian cancer if initiated earlier. Our results supported a therapeutic benefit in preventing platelet activation, degranulation, and release of Tgfβ1 in ovarian cancer. Clin Cancer Res; 23(18); 5611–21. ©2017 AACR.
ATF3 Repression of BCL-XL Determines Apoptotic Sensitivity to HDAC Inhibitors across Tumor Types
Authors: Chüeh Anderly C. , Tse Janson W.T. , Dickinson Michael , Ioannidis Paul , Jenkins Laura , Togel Lars , Tan BeeShin , Luk Ian , Davalos-Salas Mercedes , Nightingale Rebecca , Thompson Matthew R. , Williams Bryan R.G. , Lessene Guillaume , Lee Erinna F. , Fairlie Walter D. , Dhillon Amardeep S. , Mariadason John M.
Published: June 2017

Purpose:

Histone deacetylase inhibitors (HDACi) are epigenome-targeting small molecules approved for the treatment of cutaneous T-cell lymphoma and multiple myeloma. They have also demonstrated clinical activity in acute myelogenous leukemia, non–small cell lung cancer, and estrogen receptor–positive breast cancer, and trials are underway assessing their activity in combination regimens including immunotherapy. However, there is currently no clear strategy to reliably predict HDACi sensitivity. In colon cancer cells, apoptotic sensitivity to HDACi is associated with transcriptional induction of multiple immediate-early (IE) genes. Here, we examined whether this transcriptional response predicts HDACi sensitivity across tumor type and investigated the mechanism by which it triggers apoptosis.

Experimental Design:

Fifty cancer cell lines from diverse tumor types were screened to establish the correlation between apoptotic sensitivity, induction of IE genes, and components of the intrinsic apoptotic pathway.

Results:

We show that sensitivity to HDACi across tumor types is predicted by induction of the IE genes FOS, JUN, and ATF3, but that only ATF3 is required for HDACi-induced apoptosis. We further demonstrate that the proapoptotic function of ATF3 is mediated through direct transcriptional repression of the prosurvival factor BCL-XL (BCL2L1). These findings provided the rationale for dual inhibition of HDAC and BCL-XL, which we show strongly cooperate to overcome inherent resistance to HDACi across diverse tumor cell types.

Conclusions:

These findings explain the heterogeneous responses of tumor cells to HDACi-induced apoptosis and suggest a framework for predicting response and expanding their therapeutic use in multiple cancer types.
Dysphagia in Perry Syndrome: Pharyngeal Pressure in Two Cases
Authors: Umemoto George , Tsuboi Yoshio , Furuya Hirokazu , Mishima Takayasu , Fujioka Shinsuke , Fujii Naoki , Arahata Hajime , Sugahara Miwa , Sakai Mitsuaki
Published: June 2017

Background: To investigate the impact of dysphagia in Perry syndrome (PS), an autosomal dominant parkinsonism caused by mutation of DCTN1, which is associated with hypoventilation, depression, and weight loss. Case Presentation: We used tongue pressure measurements and manofluorography to investigate swallowing function in 2 patients with PS. Case 1, a 60-year-old male showing parkinsonism, and case 2, a 49-year-old male admitted with pneumonia, were diagnosed as having PS based on the DCTN1 gene analysis. Case 1 showed a pharyngeal retention of the bolus on videofluorography (VF) and a few swallows were required for its passage into the esophagus. However, tongue pressure and manometry were within the normal range. This patient could eat a normal diet under supervision. Case 2 required artificial ventilation and tube feeding on admission. The VF image showed a slow transfer of the bolus, delayed swallow reflex, and pharyngeal retention of the bolus that required several swallows for its passage into the esophagus. The tongue pressure was within the normal range, but manometry showed a significant decrease in pressure at the hypopharynx and upper esophageal sphincter. The oral intake of the patients was limited to 2 cups of jelly per day. Conclusions: The investigation of swallowing dysfunction of 2 cases of PS showed that maintaining pharyngeal pressure within the normal range was very important for oral feeding success and prognosis.
Assessing a Tool for Self-Monitoring Hydration Using Urine Color in Pregnant and Breastfeeding Women: A Cross-Sectional, Online Survey
Authors: Rigaud Marion , Sevalho Corçao Camila , Perrier Erica T. , Boesen-Mariani Sabine
Published: June 2017

Background: Pregnant and breastfeeding women experience great changes in their total body water content and water dynamics. To support the accretion of total body water during pregnancy and compensate for the water lost through breast milk during breastfeeding, increased adequate intakes (AI) for total water have been established by various health authorities. Despite this widespread advice, several studies suggest that pregnant and breastfeeding women do not meet the AI for total water, suggesting the need to raise women's awareness on the importance of adequate water intake, particularly during pregnancy and breastfeeding, as well as to provide them with a simple means of monitoring their hydration on a day-to-day basis. A urine color (UC) scale recently has been validated for hydration monitoring in pregnant and breastfeeding women. Summary: We sought to develop a version of a tool based on the UC scale, using only images or illustrations, which could be understood by users of various nationalities and spoken languages. Pregnant and breastfeeding women (n = 1,275) from Brazil, Mexico, and Poland were shown 3 versions of the tool. Understanding, appreciation, simplicity and intent to use were evaluated using a questionnaire consisting of 26 items. Key Messages: Among the 3 versions tested, one tool emerged as the most highly understood (88% spontaneous understanding) and was highly appreciated by users (mean [SD]: 8.40 [2.20] out of 10). There were no differences between countries. Furthermore, 83% reported being very likely to use the tool daily. These results suggest that a simple tool based on the UC scale will help pregnant and breastfeeding women meet the AI for total water.
Effects of Dehydration on Brain Functioning: A Life-Span Perspective
Authors: Pross Nathalie
Published: June 2017

Background: In the last 10 years, there has been an increase in the publication of literature dealing with the effects of mild dehydration on cognition in healthy adults. Fewer studies, leading to less consistent data, involved other age groups. Summary: In healthy young adults refraining from drinking or participating in dehydration protocols, it was found that mild dehydration had no impact on performance, whereas the mood was widely impaired. Several studies have also been conducted in young children either as observational studies or as interventional studies. Nevertheless, methodological differences in (de)hydration monitoring, in cognitive assessments, and in the age/brain maturation of study participants, often resulted in contradictory findings regarding the cognitive functions impacted by (de)hydration. Although not consistent, these data showed that not only mood but also performance tend to be impaired by dehydration in children. Even if older adults are likely to be more vulnerable to dehydration than younger adults, very few studies have been conducted in this regard in this population. The results show that, like it is in children, cognition tends to be impaired when the elderly are dehydrated. Taken together, these studies suggest that dehydration has greater detrimental effects in vulnerable populations. Recent imaging data suggest that the brain of children and elderly adults may have fewer resources to manage the effects of dehydration. Consequently, cognitive tasks may be more demanding for younger and older brains and performance more likely to be impaired in these populations, in comparison to young healthy subjects who have greater and more efficient resources.
Review of Rosai-Dorfman Disease: New Insights into the Pathogenesis of This Rare Disorder
Authors: Cai Yanan , Shi Zhangzhen , Bai Yuansong
Published: June 2017

Rosai-Dorfman disease (RDD) is a rare histiocytosis typically with bilateral painless cervical lymphadenopathy. Laboratory data are nonspecific, and the presence of emperipolesis in large foamy S-100+ CD1a- histiocytes is the prominent histologic feature. The pathogenesis of RDD still remains elusive. According to published studies, we propose that RDD cells might represent intermediate recruiting monocytes with differentiation blockade. Both disturbance of homoeostasis and inherent genomic alterations could contribute to initiation of the disorder through signal transduction. Several inflammatory molecules such as macrophage colony-stimulating factor, IL-1β, IL-6, and tumor necrosis factor-α also play a pivotal role in the development of this rare entity. Additional studies are needed to further elucidate the essence of the disease.
Compact Intraoperative MRI: Stereotactic Accuracy and Future Directions
Authors: Markowitz Daniel , Lin Dishen , Salas Sussan , Kohn Nina , Schulder Michael
Published: June 2017

Background: Intraoperative imaging must supply data that can be used for accurate stereotactic navigation. This information should be at least as accurate as that acquired from diagnostic imagers. Objectives: The aim of this study was to compare the stereotactic accuracy of an updated compact intraoperative MRI (iMRI) device based on a 0.15-T magnet to standard surgical navigation on a 1.5-T diagnostic scan MRI and to navigation with an earlier model of the same system. Methods: The accuracy of each system was assessed using a water-filled phantom model of the brain. Data collected with the new system were compared to those obtained in a previous study assessing the older system. The accuracy of the new iMRI was measured against standard surgical navigation on a 1.5-T MRI using T1-weighted (W) images. Results: The mean error with the iMRI using T1W images was lower than that based on images from the 1.5-T scan (1.24 vs. 2.43 mm). T2W images from the newer iMRI yielded a lower navigation error than those acquired with the prior model (1.28 vs. 3.15 mm). Conclusions: Improvements in magnet design can yield progressive increases in accuracy, validating the concept of compact, low-field iMRI. Avoiding the need for registration between image and surgical space increases navigation accuracy.
A Case of Pulmonary Langerhans Cell Sarcoma Simultaneously Diagnosed with Cutaneous Langerhans Cell Histiocytosis Studied by Whole-Exome Sequencing
Authors: Kim Si-Wook , Choi Moon Ki , Han Hye Sook , Song Hyojin , Koh Youngil , Son Seung-Myoung , Lee Ok-Jun , Lee Ji Yeoun , Lee Ki Man , Lee Ki Hyeong , Kwon Jihyun
Published: June 2017

Langerhans cell histiocytosis (LCH) and Langerhans cell sarcoma (LCS) are clonal proliferations of Langerhans-type cells. Unlike in LCH, the pathophysiology and clinical course of LCS are unclear due to its rarity. Here, we report the case of a 73-year-old male patient who was diagnosed with cutaneous LCH and pulmonary LCS at the same time. Pathological review of these 2 tumors revealed similar immunohistochemical findings. However, the tumor cells in LCS had more aggressive cytological features than those in LCH. Results of BRAF mutation analysis using real-time PCR were negative for both tumors. In whole-exome sequencing (WES), stop-gain mutations in TP53 gene were discovered only in LCS cells. The mechanism of development of LCS from various progenitor cells is currently unclear. According to the results of the WES study, changes in TP53 gene might have contributed to the malignant features of LCS.
Novel Mutation of the RUNX2 Gene in Patients with Cleidocranial Dysplasia
Authors: Hordyjewska Ewa , Jaruga Anna , Kandzierski Grzegorz , Tylzanowski Przemko
Published: June 2017

Cleidocranial dysplasia (CCD) is an autosomal dominant disorder linked to mutations in the Runt-related transcription factor 2, encoded by the RUNX2 gene, which is essential for osteoblast differentiation and skeletal development. Here, we describe a novel nonsense mutation (c.532C>T; p.Q178X) in RUNX2 identified in 3 affected members of a Polish family with CCD. The localization and transcriptional transactivation studies show that the mutated form of the protein has altered the subcellular localization and significantly decreased transactivation properties, respectively. Consequently, our data show that the c.532C>T mutation generates a defective RUNX2 protein and is genetically linked to the CCD phenotype.
Stem Cells in the Treatment of Refractory Chronic Migraines
Authors: Mauskop Alexander , Rothaus Kenneth O.
Published: June 2017

Background: Autologous adipose-derived stromal vascular fraction (SVF), which is rich in mesenchymal stromal cells, has been reported to be effective for the treatment of trigeminal neuropathic pain and chronic migraine and tension-type headaches. It is possible that stem cell activity targets neurogenic inflammation, which is a well-documented aspect of migraine pathogenesis. Methods: Adult patients with severe migraine-related disability as measured by the Migraine Disability Assessment (MIDAS) score who failed botulinum toxin injections and at least 3 prophylactic drugs were included in this study. The primary outcome measure was the change in MIDAS score 3 months after treatment. Standard liposuction was performed to obtain adipose tissue, from which SVF was isolated by centrifugation. A sample of each patient’s SVF was tested for the number of nucleated cells and their viability. Between 8 and 10 mL of SVF with 2.5–8.6 million viable cells were injected into the pericranial, neck, and trapezius muscles. Results: One man and 8 women were enrolled in the study. The mean age was 48 years, the mean duration of headaches was 16 years, the mean number of prophylactic drugs tried was 10, and the mean MIDAS score at baseline was 122. Three months after the procedure the mean MIDAS score was 88. Seven out of 9 patients had a decrease in their MIDAS score, but only 2 had meaningful improvement. Conclusion: The use of autologous adipose-derived SVF may be effective in the treatment of chronic refractory migraines. It is possible that the use of allogenic stem cells could offer a more practical and more effective approach.
PEComa with Transcription Factor E3 Overexpression: A Diagnostic and Therapeutic Challenge
Authors: Lin Richard J. , Melamed Jonathan , Wu Jennifer
Published: June 2017

PEComa with transcription factor E3 overexpression, most commonly through gene rearrangement, represents a biologically distinct subset of disease. We present here an illustrative case to highlight its diagnostic and therapeutic challenge in the context of potential pathogenic signaling pathways.
Aging of Competitive Athletes
Authors: Tanaka Hirofumi
Published: June 2017

Demographics of human aging are rapidly changing. As illustrated in the biomedicalization of aging, an ever increasing number of older adults is affected by a variety of clinical conditions and diseases, including vascular stiffening, sarcopenia, physical disability, and poor quality of life. One population that is situated in the opposite end of the health and functional spectrum to the sedentary frail elderly is Masters athletes. These older competitive athletes are endowed with substantial functional capacity, overall long-term health, high motivation, and psychosocial outlook. Masters athletes are combating the dogma and negative stereotypes of older adults and aging. From the scientific standpoint, examining Masters athletes can provide insight into preventive gerontology, primary prevention of age-related diseases and dysfunctions, and exercise-based medical practices. Moreover, the study on Masters athletes is simply joyous and entertaining as they often remind us what can be possible in aging.
AKI Adjudication: Do We Need It
Authors: Kwong Yuenting D. , Liu Kathleen D.
Published: June 2017

Adjudication, which comes from the Latin term “adjudicare” (to act as a judge), uses expert opinion to define and classify disease entities. The use of clinical adjudication may help to define more homogeneous disease subsets but comes at the expense of effort needed and generalizability. Here, we will describe the pros and cons of acute kidney injury (AKI) adjudication under varied circumstances. We will use heart failure as a paradigm and provide comparable examples from the current AKI literature.
CPT1A
Missense Mutation Associated With Fatty Acid Metabolism and Reduced Height in Greenlanders
Authors: Skotte Line , Koch Anders , Yakimov Victor , Zhou Sirui , Søborg Bolette , Andersson Mikael , Michelsen Sascha W. , Navne Johan E. , Mistry Jacqueline M. , Dion Patrick A. , Pedersen Michael L. , Børresen Malene L. , Rouleau Guy A. , Geller Frank , Melbye Mads , Feenstra Bjarke
Published: June 2017

Background—

Inuit have lived for thousands of years in an extremely cold environment on a diet dominated by marine-derived fat. To investigate how this selective pressure has affected the genetic regulation of fatty acid metabolism, we assessed 233 serum metabolic phenotypes in a population-based sample of 1570 Greenlanders.

Methods and Results—

Using array-based and targeted genotyping, we found that rs80356779, a p.Pro479Leu variant in
CPT1A
, was strongly associated with markers of
n
-3 fatty acid metabolism, including degree of unsaturation (
P
=1.16×10
−
34
), levels of polyunsaturated fatty acids,
n
-3 fatty acids, and docosahexaoenic acid relative to total fatty acid levels (
P
=2.35×10
−
15
,
P
=4.02×10
−
19
, and
P
=7.92×10
−
27
). The derived allele (L479) occurred at a frequency of 76.2% in our sample while being absent in most other populations, and we found strong signatures of positive selection at the locus. Furthermore, we found that each copy of L479 reduced height by an average of 2.1 cm (
P
=1.04×10
−
9
). In exome sequencing data from a sister population, the Nunavik Inuit, we found no other likely causal candidate variant than rs80356779.

Conclusion—

Our study shows that a common
CPT1A
missense mutation is strongly associated with a range of metabolic phenotypes and reduced height in Greenlanders. These findings are important from a public health perspective and highlight the usefulness of complex trait genetic studies in isolated populations.
Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model
Authors: Gevaert Andreas B. , Shakeri Hadis , Leloup Arthur J. , Van Hove Cor E. , De Meyer Guido R.Y. , Vrints Christiaan J. , Lemmens Katrien , Van Craenenbroeck Emeline M.
Published: June 2017

Background—

Because of global aging, the prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated to play a central role. Cellular senescence is a process of cellular growth arrest linked with aging and inflammation. We used mice with accelerated aging to investigate the role of cellular senescence in HFpEF development.

Methods and Results—

Senescence-accelerated mice (SAM, n=18) and control mice with normal senescence (n=15) were fed normal chow or a high-fat, high-salt diet (WD). Vascular and cardiac function was assessed at 8, 16, and 24 weeks of age. At 24 weeks, both SAM on WD (SAM-WD) and SAM on regular diet displayed endothelial dysfunction, as evidenced by impaired acetylcholine-induced relaxation of aortic segments and reduced basal nitric oxide. At week 24, SAM-WD had developed HFpEF, characterized by diastolic dysfunction, left ventricular hypertrophy, left atrial dilatation, and interstitial fibrosis. Also, exercise capacity was reduced and lung weight increased. Cardiovascular inflammation and senescence were assessed by immunohistochemical and immunofluorescence staining of hearts and aortas. SAM-WD showed increased endothelial inflammation (intercellular adhesion molecule 1 expression) and increased endothelial senescence (acetyl-p53/CD31 costaining). The latter correlated with diastolic function and intercellular adhesion molecule 1 expression.

Conclusions—

SAM develop endothelial dysfunction. Adding a high-salt, high-fat diet accelerates endothelial senescence and instigates endothelial inflammation. This coincides with hemodynamic and structural changes typical of HFpEF. Targeting endothelial senescence could be a new therapeutic avenue in HFpEF.
Success, Failure, and Transparency in Biomarker-Based Drug Development
Authors: Hey Spencer Phillips , Franklin Jessica M. , Avorn Jerry , Kesselheim Aaron S.
Published: June 2017

Background—

Although biomarkers are used as surrogate measures for drug targeting and approval and are generally based on plausible biological hypotheses, some are found to not correlate well with clinical outcomes. Over-reliance on inadequately validated biomarkers in drug development can lead to harm to trial subjects and patients and to research waste. To shed greater light on the process and ethics of biomarker-based drug development, we conducted a systematic portfolio analysis of cholesterol ester transfer protein inhibitors, a drug class designed to improve lipid profiles and prevent cardiovascular events. Despite years of development, no cholesterol ester transfer protein inhibitor has yet been approved for clinical use.

Methods and Results—

We searched PubMed and Clinicaltrials.gov for clinical studies of 5 known cholesterol ester transfer protein inhibitors: anacetrapib, dalcetrapib, evacetrapib, TA-8995, and torcetrapib. Published reports and registration records were extracted for patient demographic characteristics and study authors’ recommendations of clinical usage or further testing. We used Accumulating Evidence and Research Organization graphing to depict the portfolio of research activities and a Poisson model to examine trends. We identified 100 studies for analysis that involved 96 944 human subjects. The data from only 41 201 (42%) of the human subjects had been presented in a published report. For the 3 discontinued cholesterol ester transfer protein inhibitors, we found a pattern of consistently positive results on lipid-modification end points followed by negative results using clinical end points.

Conclusions—

Inefficiencies and harms can arise if a biomarker hypothesis continues to drive trials despite successive failures. Regulators, research funding bodies, and public policy makers may need to play a greater role in evaluating and coordinating biomarker-driven research programs.
Epidemiology, Endovascular Treatment, and Prognosis of Cerebral Venous Thrombosis: US Center Study of 152 Patients
Authors: Salottolo Kristin , Wagner Jeffrey , Frei Donald F. , Loy David , Bellon Richard J. , McCarthy Kathryn , Jensen Judd , Fanale Christopher , Bar‐Or David
Published: June 2017

Background

Cerebral venous thrombosis is a rare cause of stroke that poses diagnostic, therapeutic, and prognostic challenges. Mainstay treatment is systemic anticoagulation, but endovascular treatment is increasingly advocated. Our objectives were to describe the epidemiology, treatment, and prognosis of 152 patients with cerebral venous thrombosis.

Methods and Results

This was a retrospective study of consecutive cerebral venous thrombosis cases from 2006 to 2013 at a comprehensive stroke center through hospital discharge. Predictors of full recovery (modified Rankin Scale scores 0–1) were analyzed with multiple logistic regression and presented as adjusted odds ratios (
AORs
) with 95% confidence intervals (
CIs
). The population was young (average age: 42 years), majority female (69%), and commonly presenting with cerebral edema (63%), and 72% were transferred in. All patients received systemic anticoagulation; 49% (n=73) required endovascular treatment. Reasons for requiring endovascular treatment included cerebral edema, herniation, or hemorrhagic infarct (n=38); neurologic decline (n=17); rethrombosis, persistent occlusion, or clot propagation (n=10); extensive clot burden (n=7); and persistent headache despite anticoagulation (n=1). There were 7 (10%) procedural complications. Recanalization was successful (61%), partial (30%), and unsuccessful (9%). Overall, 60% fully recovered. Positive predictors of full recovery included hormonal etiology, particularly for patients who were transferred in (
AOR
: 7.06 [95% CI, 2.27–21.96], interaction
P
=0.03) and who had migraine history (
AOR
: 4.87 [95% CI, 1.01–23.50],
P
=0.05), whereas negative predictors of full recovery were cerebral edema (
AOR
: 0.11 [95% CI, 0.04–0.34],
P
<0.001) and motor weakness (
AOR
: 0.28 [95% CI, 0.09–0.96],
P
=0.04).

Conclusions

As one of the largest cohort studies, our findings suggest that cerebral edema, history of migraine, and hormonal etiology were prognostic and that endovascular treatment might be a safe and effective treatment for cerebral venous thrombosis when conventional management is inadequate.
Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2‐Hour Infusion in High‐Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention
Authors: Marian Moazez J. , Alli Oluseun , Al Solaiman Firas , Brott Brigitta C. , Sasse Mark , Leesar Tara , Prabhu Sumanth D. , Leesar Massoud A.
Published: June 2017

Background

In patients with non‐
ST
‐segment elevation acute coronary syndromes, inhibition of platelet aggregation (
IPA
) with a potent P2Y
12
inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein
II
b/
III
a inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but
IPA
with ticagrelor and eptifibatide bolus versus 2‐hour infusion is unknown.

Methods and Results

A total of 70 P2Y
12
‐naïve patients, with high‐risk non‐
ST
‐segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2‐hour infusion (group 2). Levels of
IPA
with
ADP
, thrombin receptor‐activating peptide, collagen, and high on‐treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point,
IPA
with
ADP
20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 (
P
<0.001 for noninferiority). High on‐treatment platelet reactivity with
ADP
was zero at 2, 6, and 24 hours in both groups.
IPA
levels with
ADP
, thrombin receptor‐activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively;
P
<0.01).

Conclusions

Ticagrelor and eptifibatide bolus maximally inhibited platelet aggregation at 2 hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2‐hour infusion and might decrease bleeding complications.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01919723.
Exercise‐Related Out‐of‐Hospital Cardiac Arrest Among the General Population in the Era of Public‐Access Defibrillation: A Population‐Based Observation in Japan
Authors: Kiyohara Kosuke , Nishiyama Chika , Kiguchi Takeyuki , Nishiuchi Tatsuya , Hayashi Yasuyuki , Iwami Taku , Kitamura Tetsuhisa
Published: June 2017

Background

Exercise can trigger sudden cardiac arrest. Early initiation of cardiopulmonary resuscitation and automated external defibrillator use by laypersons could maximize the survival rate following exercise‐related out‐of‐hospital cardiac arrest (
OHCA
).

Methods and Results

OHCA
data between 2005 and 2012 were obtained from a prospective population‐based
OHCA
registry in Osaka Prefecture. Patients with
OHCA
of presumed cardiac origin and occurring before emergency medical service personnel arrival were included. The incidence trends of exercise‐related
OHCA
over the 8‐year study period were assessed. Among patients with bystander‐witnessed, exercise‐related
OHCA
, the trends in the initiation of bystander cardiopulmonary resuscitation, public‐access defibrillation, and outcome were evaluated. The primary outcome was 1‐month survival with favorable neurological outcome, defined as cerebral performance category 1 or 2. During the study period, 0.7% of
OHCAs
of cardiac origin (222/31 030) were exercise related. The incidence of exercise‐related
OHCA
increased from 1.8 (per million population per year) in 2005 to 4.3 in 2012. Of these, 83.8% (186/222) were witnessed by bystanders. Among the patients with bystander‐witnessed, exercise‐related
OHCA
, the proportion that received bystander cardiopulmonary resuscitation (50.0% in 2005 and 86.2% in 2012) and public‐access defibrillation (7.1% in 2005 and 62.1% in 2012) significantly increased during the study period. Furthermore, the rate of 1‐month survival with favorable neurological outcome among these patients significantly improved (from 28.6% in 2005 to 58.6% in 2012).

Conclusions

The incidence rate of exercise‐related
OHCA
was low in the study population. The increase in bystander cardiopulmonary resuscitation and public‐access defibrillation rates were associated with improved outcome among patients with bystander‐witnessed, exercise‐related
OHCA
.
Resurrecting the Body Politic – Physiology’s Influence on Sir William Petty’s Political Arithmetick
Authors: Sivado Akos
Published: June 2017

Sir William Petty (1623-1687), the founder of the method of “political arithmetick,” was a trained physician and anatomist. Receiving medical education both in England and on the continent, he later turned away from an academic career and a medical practice in favour of dealing with political and social matters, becoming one of the first advocates of quantifying social phenomena in order to better govern a population. Offering his services to both Oliver Cromwell and Charles II, Petty sought to reform and transform society (in Ireland in particular), while considering the physician’s treatment of natural bodies and the political advisor’s treatment of the body politic to be analogous enterprises. In doing so, he did not refrain from suggesting serious interventions into social life – something that his contemporary peers did not consider compatible with their medical backgrounds. This article attempts to investigate how Petty’s proposals could have differed so much in their scope and content from those of his colleagues, while remaining true to their largely shared Baconian and Harveyan origins.
A Chemistry of Human Nature: Chemical Imagery in Hume’s Treatise
Authors: Demeter Tamás
Published: June 2017

David Hume’s ‘science of man’ is frequently interpreted as an enterprise inspired in crucial respects by Newton’s Principia. However, a closer look at Hume’s central concepts and methodological commitment suggests that his Treatise of Human Nature is much more congruent with the research traditions that arose in the wake of Newton’s Opticks. In this paper I argue that the label Hume frequently attached to his project, ‘anatomy of the mind,’ is a metaphor that, considered in itself, seems to be expressing a commitment to the study of human nature in analogy with organic living nature. In this vein, Hume’s anatomy relies on conceptual and methodological resources derived from a chemical and physiological perspective on the natural cognitive and affective functioning of human beings. Since the idea of natural functioning provides various options for deriving normative considerations, Hume’s account can be seen as a middle-range theory that connects the discourses of organic nature and normative morality.
The Natural, the Pragmatic and the Moral in Kant’s Anthropology: The Case of Temperaments
Authors: Cohen Alix
Published: June 2017

This paper explores the interconnections between the normative and the descriptive dimensions of Kant’s anthropology. It suggests that, far from being independent of each other or even excluding each other, as is often presupposed, the normative standpoint necessitates the explanatory one. To support this claim, I discuss the case of human temperaments and show in what sense a necessary component of pragmatic anthropology consists in the naturalistic study of human nature – what Kant calls “what nature makes of the human being.”1
Religiousness in First-Episode Psychosis
Authors: Hanevik Hilde , Hestad Knut A. , Lien Lars , Joa Inge , Larsen Tor Ketil , Danbolt Lars Johan
Published: June 2017

The aim of the present study is to explore the significance of religiousness for patients suffering from first-episode psychosis. Our study is a thematic analysis. The study illustrates how the patients understood their hallucinations as mystical experiences. Even so, many of the patients describe their religiousness to be helpful in coping with their disorder, giving meaning to life as well as a relationship to a sacred figure. However, their religiousness often contained religious omnipotent delusions, and built on hallucinations, displayed an unsecure relationship to the sacred figure. From a psychiatric point of view, the misinterpretation of hallucinations as mystical experiences may reinforce their delusional system and cause an obstacle to recovery. This misinterpretation may also cause problems for patients’ religious coping. Our findings underline the importance of taking patients’ religiousness into account in psychotherapy.
The Mud and the Water: Towards a History of a Simile in Kabbalah
Authors: Idel Moshe
Published: June 2017

The present study surveys a series of kabbalistic antecedents of a simile for the presence of the roots of evil in the pre-emanationalist stage, as formulated in Lurianic Kabbalah. What has been conceived by scholars as a cathartic explanation characteristic of Lurianism, and even an esoteric aspect of this Kabbalah, turns to be quite an exoteric teaching shared by several kabbalists since the 13th century.
From the ‘Book to Read’ to the ‘Book to Collect’: Harry Potter and digital platforms in France
Authors: Nicolas Agathe
Published: June 2017

Online presentations of printed books have led to a complete transformation of publishers’ work, books’ status, and readers’ habits. Through their webpages, publishers invite visitors to create communities, to join social networks, to communicate their likes and dislikes. Everything about the digital presentation of printed books makes manifest the online existence of both readers and books. How, then, can printed books not only compete, but also evolve and become more visible, by means of digital tools and platforms? This article seeks answers to this question by asking: Through their digital tools are publishers’ webpages placing value on literature or on communication? Are digital platforms transforming the objet-livre (the physical object of the book) from a tool into a work of art? And are they transforming visitors from readers into collectors?
What Were the Process and Response of University Staff and Students to the Availability of a Shared Reading Scheme for Those Embarking on a University Education?: A case study
Authors: Baverstock Alison , Steinitz Jackie , Bryars Laura
Published: June 2017

This paper reports and reflects on the processes and outcomes of a shared reading programme targeted at new students embarking on a university qualification at Kingston University. It isolates the various stages involved, from selecting a book for sharing, to the despatch of a bespoke edition to new students and wider distribution within the institution. It then explores and assesses the effects the scheme had on the community, by role and department, through both informal measures of impact and post-delivery surveying of those involved. Recommendations are offered for further development of the project.
Taxonomic study of the leafhopper genera Farynala Dworakowska and Xaniona Zhang & Huang (Hemiptera: Cicadellidae: Typhlocybinae: Typhlocybini), with descriptions of three new species from China
Authors: YAN BIN , YANG MAO-FA
Published: June 2017

Two new species of the genus Farynala Dworakowska, 1970 and one new species of the genus Xaniona Zhang & Huang, 2005 are described and illustrated: F. dextra sp. nov., F. sinistra sp. nov. and X. falcata sp. nov.. Keys and checklists of genera are provided. The type specimens are deposited in the Institute of Entomology, Guizhou University, Guiyang, China (GUGC).
A new species of Wolf Snake of the genus Lycodon H. Boie in Fitzinger (Squamata: Colubridae) from the Aceh Province of northern Sumatra, Indonesia
Authors: WOSTL ELIJAH , HAMIDY AMIR , KURNIAWAN NIA , SMITH ERIC N.
Published: June 2017

Herein we describe a new species of Lycodon H. Boie in Fitzinger (Squamata: Colubridae) from Aceh Province, Sumatra. This brings the number of species known to occur on the Sunda Shelf to seven. The new species is readily diagnosed from the other congeners in the region by the lack of a preocular scale, the presence of keeled dorsal scales and a banded venter. It is superficially similar to L. butleri from the Malaysian Peninsula in coloration and to L. subcinctus in head scalation. Genetically, the new species is most similar to a group of species from Mainland Southeast Asia and China. We also note the presence of several deeply divergent lineages within Lycodon that may warrant the recognition as distinct genera. The genus is in need of a comprehensive molecular and morphological review.
A new species of Calyptotheca (Bryozoa: Cheilostomata) from Alexandria, Egypt, southeastern Mediterranean
Authors: ABDELSALAM KHALED M. , TAYLOR PAUL D. , DORGHAM MOHAMED M.
Published: June 2017

Beginning in December 2015, an unknown bryozoan with large, deep-orange colonies began to appear in the Eastern Harbour of Alexandria, Egypt. Here we identify the species as belonging to the predominantly Indo-Pacific cheilostome genus Calyptotheca Harmer, 1957 and describe it as a new species, Calyptotheca alexandriensis n. sp. The new species exhibits intensive growth sporadically on different hard substrata, including rocks, submerged concrete walls, ropes, ships’ hulls, and metal pipes supporting marina piers. It is restricted to the Eastern Harbour, particularly in shallow parts, with the densest aggregations on the metal pier supports. The source of this bryozoan is enigmatic but most likely involved introduction by shipping.
Randomised controlled trial of a healthy lifestyle intervention among smokers with psychotic disorders: Outcomes to 36 months
Authors: Baker Amanda L , Richmond Robyn , Kay-Lambkin Frances J , Filia Sacha L , Castle David , Williams Jill M , Lewin Terry J , Clark Vanessa , Callister Robin , Palazzi Kerrin
Published: June 2017

Objective:

People living with psychotic disorders (schizophrenia spectrum and bipolar disorders) have high rates of cardiovascular disease risk behaviours, including smoking, physical inactivity and poor diet. We report cardiovascular disease risk, smoking cessation and other risk behaviour outcomes over 36 months following recruitment into a two-arm randomised controlled trial among smokers with psychotic disorders.

Methods:

Participants ( N = 235) drawn from three sites were randomised to receive nicotine replacement therapy plus (1) a Healthy Lifestyles intervention delivered over approximately 9 months or (2) a largely telephone-delivered intervention (designed to control for nicotine replacement therapy provision, session frequency and other monitoring). The primary outcome variables were 10-year cardiovascular disease risk and smoking status, while the secondary outcomes included weekly physical activity, unhealthy eating, waist circumference, psychiatric symptomatology, depression and global functioning.

Results:

Significant reductions in cardiovascular disease risk and smoking were detected across the 36-month follow-up period in both intervention conditions, with no significant differences between conditions. One-quarter (25.5%) of participants reported reducing cigarettes per day by 50% or more at multiple post-treatment assessments; however, few (8.9%) managed to sustain this across the majority of time points. Changes in other health behaviours or lifestyle factors were modest; however, significant improvements in depression and global functioning were detected over time in both conditions. Participants experiencing worse ‘social discomfort’ at baseline (e.g. anxiety, mania, poor self-esteem and social disability) had on average significantly worse global functioning, lower scores on the 12-Item Short Form Health Survey physical scale and significantly greater waist circumference.

Conclusion:

Although the telephone-delivered intervention was designed as a comparison condition, it achieved excellent retention and comparable outcomes. Telephone-delivered smoking cessation support may potentially help to reduce smoking rates among people with psychotic disorders. Discomfort in social situations may also be a useful target for future health interventions, addressing confidence and social skills, and promoting social networks that reduce inactivity.
The Soothing Sea: A Virtual Coastal Walk Can Reduce Experienced and Recollected Pain
Authors: Tanja-Dijkstra Karin , Pahl Sabine , White Mathew P. , Auvray Melissa , Stone Robert J. , Andrade Jackie , May Jon , Mills Ian , Moles David R.
Published: June 2017

Virtual reality (VR) distraction has become increasingly available in health care contexts and is used in acute pain management. However, there has been no systematic exploration of the importance of the content of VR environments. Two studies tested how interacting with nature VR influenced experienced and recollected pain after 1 week. Study 1 ( n = 85) used a laboratory pain task (cold pressor), whereas Study 2 ( n = 70) was a randomized controlled trial with patients undergoing dental treatment. In Study 1, nature (coastal) VR reduced both experienced and recollected pain compared with no VR. In Study 2, nature (coastal) VR reduced experienced and recalled pain in dental patients, compared with urban VR and standard care. Together, these data show that nature can improve experience of health care procedures through the use of VR, and that the content of the VR matters: Coastal nature is better than urban.
Welfare regime analysis: 30 years in the making
Authors: Aspalter Christian
Published: June 2017

This article analyses the past two and a half decades of welfare regime analysis in comparative social policy, particularly referring to the avalanche of research studies set off by Esping-Andersen’s book The Three Worlds of Welfare Capitalism, and the main developments it led to in terms of developing welfare regime theories, with special reference to the development of ideal types. The article applies the method of developing social policy theory, in particular ideal-typical welfare regime theory. It looks at the differences between the theory (and method) of using ‘ideal types’ and the ones that rely on ‘real types’. In particular, the study will discuss different choices and ways of how to develop ideal types in comparative welfare regime analysis.
Effect of volume fraction of reinforcement phase on mechanical behavior of ultra-high-temperature composite consisting of iron matrix and TiB2 particulates
Authors: Jahani Babak , Salimi Jazi Mehdi , Azarmi Fardad , Croll Andrew
Published: June 2017

Recently, ultra-high-temperature ceramics have received abundance attention due to growing demand of new materials for extreme service conditions. In this study, titanium diboride particles as an ultra-high-temperature ceramic material have been used to reinforce iron matrix to fabricate a metal matrix composite. Iron–titanium diboride composite samples with different volume fractions of titanium diboride fabricated using powder metallurgy route. Physical, microstructural and mechanical properties of metal matrix composite were studied. The results indicated that addition of titanium diboride only up to 20 vol% increased mechanical properties of the processed composite. Microstructure-based finite element analysis could verify the experimental results.