bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Triage Strategies for HPV-Positive Women: Canadian Cervical Cancer Screening Trial Results
Authors: Isidean Sandra D. , Mayrand Marie-Hélène , Ramanakumar Agnihotram V. , Rodrigues Isabel , Ferenczy Alex , Ratnam Sam , Coutlée François , Franco Eduardo L.
Published: January 2017

Background: High-risk human papillomavirus (HR-HPV) testing has become a preferred cervical cancer screening strategy in some countries due to its superior sensitivity over cytology-based methods for identifying cervical intraepithelial neoplasia of grade 2 or worse (CIN2+). Improved sensitivity has been accompanied by reductions in specificity and concerns regarding overscreening and overtreatment of women with transient or nonprogressing HR-HPV infections. Triage of HR-HPV+ women to colposcopy is, thus, warranted for appropriate management and treatment.

Methods: Using data from the Canadian Cervical Cancer Screening Trial (CCCaST), we compared the performance of cytology and HR-HPV strategies to detect CIN2+ among HR-HPV+ women (age, 30–69 years). Colposcopy referral rates and performance gains from adding other HR-HPV genotypes to HPV16/18+ triage were also evaluated.

Results: A strategy referring all women HPV16/18+ and HPV16/18−, but with atypical squamous cells of undetermined significance or worse cytology (ASC-US+) had the highest sensitivity [82.5%; 95% confidence interval (CI), 70.9%–91.0%] but yielded the highest colposcopy referral rate. HPV16/18+ triage was the next most sensitive strategy (64.1%; 95% CI, 51.1%–75.7%). Low-grade squamous intraepithelial lesion or worse cytology (LSIL+) triage yielded a low sensitivity (32.8%; 95% CI, 21.9%–45.4%) but had the most favorable specificity (93.6%; 95% CI, 91.0%–95.6%), positive predictive value (41.5%; 95% CI, 28.1%–55.9%), and colposcopy referral rate of strategies examined. HPV viral load triage strategies did not perform optimally overall. Inclusion of HR-HPV genotypes 31 and 52 to HPV16/18+ triage provided the highest sensitivities.

Conclusion: Concerns surrounding HPV-based screening can be effectively mitigated via triage.

Impact: Balancing the benefits of HPV-based primary cervical screening with informed management recommendations for HR-HPV+ women may decide the success of its widening utilization. Cancer Epidemiol Biomarkers Prev; 26(6); 923–9. ©2017 AACR.
In Hepatocellular Carcinoma miR-221 Modulates Sorafenib Resistance through Inhibition of Caspase-3–Mediated Apoptosis
Authors: Fornari Francesca , Pollutri Daniela , Patrizi Clarissa , La Bella Tiziana , Marinelli Sara , Casadei Gardini Andrea , Marisi Giorgia , Baron Toaldo Marco , Baglioni Michele , Salvatore Veronica , Callegari Elisa , Baldassarre Maurizio , Galassi Marzia , Giovannini Catia , Cescon Matteo , Ravaioli Matteo , Negrini Massimo , Bolondi Luigi , Gramantieri Laura
Published: January 2017

Purpose: The aberrant expression of miR-221 is a hallmark of human cancers, including hepatocellular carcinoma (HCC), and its involvement in drug resistance, together with a proved in vivo efficacy of anti-miR-221 molecules, strengthen its role as an attractive target candidate in the oncologic field. The discovery of biomarkers predicting the response to treatments represents a clinical challenge in the personalized treatment era. This study aimed to investigate the possible role of miR-221 as a circulating biomarker in HCC patients undergoing sorafenib treatment as well as to evaluate its contribution to sorafenib resistance in advanced HCC.

Experimental Design: A chemically induced HCC rat model and a xenograft mouse model, together with HCC-derived cell lines were employed to analyze miR-221 modulation by Sorafenib treatment. Data from the functional analysis were validated in tissue samples from surgically resected HCCs. The variation of circulating miR-221 levels in relation to Sorafenib treatment were assayed in the animal models and in two independent cohorts of patients with advanced HCC.

Results: MiR-221 over-expression was associated with Sorafenib resistance in two HCC animal models and caspase-3 was identified as its target gene, driving miR-221 anti-apoptotic activity following Sorafenib administration. Lower pre-treatment miR-221 serum levels were found in patients subsequently experiencing response to Sorafenib and an increase of circulating miR-221 at the two months assessment was observed in responder patients.

Conclusions: MiR-221 might represent a candidate biomarker of likelihood of response to Sorafenib in HCC patients to be tested in future studies. Caspase-3 modulation by miR-221 participates to Sorafenib resistance. Clin Cancer Res; 23(14); 3953–65. ©2017 AACR.
Activation of TRPA1 Channel by Antibacterial Agent Triclosan Induces VEGF Secretion in Human Prostate Cancer Stromal Cells
Authors: Derouiche Sandra , Mariot Pascal , Warnier Marine , Vancauwenberghe Eric , Bidaux Gabriel , Gosset Pierre , Mauroy Brigitte , Bonnal Jean-Louis , Slomianny Christian , Delcourt Philippe , Dewailly Etienne , Prevarskaya Natalia , Roudbaraki Morad
Published: January 2017

Accruing evidence indicates that exposure to environmental compounds may adversely affect human health and promote carcinogenesis. Triclosan (TCS), an antimicrobial agent widely used as a preservative in personal care products, has been shown to act as an endocrine disruptor in hormone-dependent tissues. Here, we demonstrate a new molecular mechanism by which TCS stimulates the secretion by human prostate cancer stromal cells of vascular endothelial growth factor (VEGF), a factor known to promote tumor growth. This mechanism involves an increase in intracellular calcium levels due to the direct activation of a membrane ion channel. Using calcium imaging and electrophysiology techniques, we show for the first time that environmentally relevant concentrations of TCS activate a cation channel of the TRP family, TRPA1 (Transient Receptor Potential Ankirin 1), in primary cultured human prostate cancer stromal cells. The TCS-induced TRPA1 activation increased basal calcium in stromal cells and stimulated the secretion of VEGF and epithelial cells proliferation. Interestingly, immunofluorescence labeling performed on formalin-fixed paraffin-embedded prostate tissues showed an exclusive expression of the TRPA1 channel in prostate cancer stromal cells. Our data demonstrate an impact of the environmental factor TCS on the tumor microenvironment interactions, by activating a tumor stroma-specific TRPA1 ion channel. Cancer Prev Res; 10(3); 177–87. ©2017 AACR.
Involvement of XBP1s in Blue Light-Induced A2E-Containing Retinal Pigment Epithelium Cell Death
Authors: Lu Bing , Zhang Pengfei , Zhou Minwen , Wang Wenqiu , Gu Qing , Feng Jingyang , Luo Xueting , Sun Xiangjun , Wang Fenghua , Sun Xiaodong
Published: January 2017

Purpose: Retinal pigment epithelium (RPE) cell dysfunction is essential to the development of retinal degenerative disease. This study was designed to investigate how spliced X-box-binding protein 1 (XBP1s) regulates different modes of RPE cell death in vitro. Methods: Human ARPE19 cells were incubated with 25 μM N-retinylidene-N-retinylethanolamine (A2E) and irradiated with blue light. Expressions of glucose-regulated protein 78 (GRP78) and XBP1s were detected by real-time quantitative PCR and Western blot. STF-083010 was used to suppress XBP1s expression. ARPE19 cell apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling and flow cytometry. Receptor-interacting protein kinase-3 (RIP3) was detected by Western blot. Changes in the morphology of ARPE19 cells were identified by transmission electron microscopy. Results: Blue light-induced A2E-containing ARPE19 cell damage caused a transient elevation of GRP78 and XBP1s, while RIP3 rose in the late stage. STF-083010 effectively inhibited XBP1s expression and brought about the aggravation of apoptosis together with an alleviation of RIP3 expression. Most of the dying cells exhibited apoptotic morphology. Conclusion: A2E, along with blue light, brought about apoptosis and necroptosis of ARPE19 cells, and XBP1s was transiently elevated. The suppression of XBP1s induced ARPE19 cell death by promoting apoptosis rather than necroptosis. XBP1s might play a role in the pathogenesis of retinal degenerative diseases.
Quality of Life after Intestinal Resection in Patients with Crohn Disease: A Systematic Review
Authors: Ha Francis J. , Thong Louisa , Khalil Hanan
Published: January 2017

Background/Aims: Most patients with Crohn disease (CD) require surgery within 10 years of diagnosis. Intestinal resection is the most commonly performed operation although the effects on health-related quality of life (HRQOL), particularly long-term, are contentious. Methods: We conducted a systematic review evaluating the impact of intestinal resection on the HRQOL of CD patients, predictors of postoperative HRQOL, and patient satisfaction with surgery. Results: Nine studies including 1,108 CD patients undergoing intestinal resection were identified as eligible for inclusion. The median age at surgery was 29-41 years with varying follow-up period (range 30 days-5 years). Ileocolic resection was the most commonly performed operation on an elective basis (range 95-100%). HRQOL improved as early as 2 weeks postoperatively and lasted up to 5 years across both generic and gastrointestinal domains. Gender, smoking, and disease recurrence were potential predictors of postoperative HRQOL. Patient satisfaction is high with regard to surgery, with preference for a laparoscopic approach. Conclusion: Intestinal resection in CD patients improved HRQOL in the short- and long-term and patients describe high satisfaction about their surgery. Further studies are needed to validate potential predictors of postoperative HRQOL in this cohort.
Risk of Intracranial Hemorrhage after Endovascular Treatment for Acute Ischemic Stroke: Systematic Review and Meta-Analysis
Authors: Hao Yonggang , Zhang Zhizhong , Zhang Hao , Xu Lili , Ye Zusen , Dai Qiliang , Liu Xinfeng , Xu Gelin
Published: January 2017

Background: Intracranial hemorrhage is a major complication of endovascular treatment in patients with acute ischemic stroke. Controlled clinical trials reported varied incidences of intracranial hemorrhage after endovascular treatment. This meta-analysis aimed to estimate whether endovascular treatment, compared with medical treatment, increases the risk of intracranial hemorrhage in patients with acute ischemic stroke. Methods: The current publications on endovascular treatment for acute ischemic stroke were systematically reviewed. Rates of intracranial hemorrhage after endovascular treatment for acute ischemic stroke reported in controlled clinical trials were pooled and analyzed. Random and fixed-effect models were used to pool the outcomes. For analyzing their individual risks, intracranial hemorrhages after endovascular treatment were classified as symptomatic and asymptomatic. Results: Eleven studies involving 1,499 patients with endovascular treatment and 1,320 patients with medical treatment were included. After pooling the data, the risk of any intracranial hemorrhage was significantly higher in patients with endovascular treatment than in patients with medical treatment (35.0 vs. 19.0%, OR = 2.55, 95% CI: 1.64-3.97, p < 0.00001). The risk of asymptomatic intracranial hemorrhage was also significantly higher in patients with endovascular treatment than in those with medical treatment (28 vs. 12%, OR = 3.16, 95% CI: 1.62-6.16, p < 0.001). However, the risks of symptomatic intracranial hemorrhage were similar in patients with endovascular treatment and in those with medical treatment (5.6 vs. 5.2%, OR = 1.09, 95% CI: 0.79-1.50, p = 0.61). Conclusion: Although the risk of any intracranial hemorrhage may increase after endovascular treatment, the risk of symptomatic intracranial hemorrhage may remain similar as compared with medical treatment.
Simultaneous Kissing Stenting: A Valuable Technique for Reconstructing the Stenotic Initial Segment of the Right Subclavian Artery
Authors: Zhang Ping , Chen Daiqi , Tian Daishi , Zhang Qiang , Wang Minghuan , Li Qian , Luo Xiang
Published: January 2017

Atherosclerotic stenosis or occlusion often involves the subclavian artery. For lesions that are close to the orifice of the right subclavian artery, stenting of the right subclavian artery itself blocks the pathway from the innominate artery to the right carotid artery and causes problems in patients with multiple angiostenosis, especially involving the right carotid system. In this study, we report 2 cases using simultaneous kissing stenting (SKS) of the right subclavian artery and the right carotid artery to relieve right subclavian stenosis and maintain right carotid system patency. Standard stenting methods were used to perform SKS. Two self-expanding stents were implanted simultaneously into the initial segment of the right subclavian artery and the right carotid artery, forming a “Y” shape, with the overlap of the proximal segments in the innominate artery ≥5 mm. After SKS, the stenosed right subclavian artery was dilated, and the patency of the right carotid system was maintained. The symptoms of patients were relieved and the stents were intact at several months of follow-up. In conclusion, SKS of the right subclavian artery and the right carotid artery might be a safe and effective procedure when the stenotic or occlusive lesion in the initial segment of the right subclavian artery is close to the orifice, and lesions (or potential ones) exist in the right carotid system.
Delay in diagnosis of breast cancer in a public oncologic hospital
Authors: Tramonte Maiara S. , Silva Priscila C. S. , Chubaci Silvana R. , Cordoba Camila C. R. C. , Zucca-Matthes Gustavo , Vieira René A. C.
Published: January 2017

Study model: A prospective, observational, transversal study. Objective: To evaluate the main factors related to delayed diagnosis of breast cancer. Method: A structured questionnaire was performed at the first clinical consultation, evaluating factors related to delayed in the diagnosis of breast cancer. Results: 156 women were selected for the study, where the majority had low education (58.9%), aged between 40 and 69 years (73.1%), lack of knowledge about breast self-examination (55.8 %) and no regularity of mammography (52.6%). 72.4 % had tumor at advanced stage at diagnosis. There was an association between delayed diagnosis and age. The multiple regression model adjusted for by age, showed increase risk related to health system (OR= 3.08), education (OR=5.46) and adherence (OR=5.67) were associated with late clinical stage at diagnosis. Conclusion: The factors related to advanced stage at diagnosis are linked and multiples. It indicates the necessity to perform strategies related to increase the adherence to mammography
Effects of methylphenidate on auditory processing assessment: a case study
Authors: Melo Ândrea de , Oppitz Sheila Jacques , Gois Marjana , Garcia Michele Vargas , Biaggio Eliara Pinto Vieira
Published: January 2017

Model of the study: case report. Introduction: The Auditory Processing Disorder (APS) and Attention Deficit Hyperactivity Disorder (ADHD) show similarity for signs and symptoms, however are unique and comorbidities may be presented correlated. Importance of the study: APD and ADHD present similar symptoms and may be correlated, but there is a need for differential diagnosis between such comorbidities to improve the quality of life of the subject. Purpose: This study analyzed the results of the auditory processing assessment in a subject with attention deficit, before and after use of the Methylphenidate medicine. Methods: It was used a battery of behavioral tests of auditory processing and the LongLatency Auditory Evoked Potential (LLAEP) in two different moments, before and after pharmacological treatment for attention deficit disorder. Comments: Participated on this study a subject of 22 years assessed in the Audiology Clinic of a University Hospital, because reported comprehension difficulty of speech in noise. The clinical history showed perinatal complications (prematurity, low birth weight, remain in neonatal ICU) and attention complaints over the years. Results: The results tests showed that there was a subtle improvement in performance during behavioral assessment of auditory processing, as well as in the electrophysiological assessment after the medication methylphenidate. Conclusion: These results emphasize the speech therapists/audiologists about the need to consider the use of medication methylphenidate by the patient at the time of auditory processing evaluation, as well as therapeutic process
Laparoscopic treatment of bowel obstruction as a late presentation of traumatic diaphagmatic hernia: case report
Authors: Diniz Ianê C. , Rodrigues Milena M. , Silva Thainá S. M. , Lucena Carolina B. , Barbosa Fábio Colagrossi Paes
Published: January 2017

Design of the study: Case report. Objectives: To present, through a case report, a post-traumatic diaphragmatic hernia with late diagnosis and reinforce the importance of systematic research of diaphragmatic injury in thoracoabdominal trauma. Relevance: the incidence of post traumatic diaphragmatic hernia in polytrauma is 8% and presents little morbidity if diagnosed at the time of trauma. However, the morbidity increases significantly if it is diagnosed late. Surgical repair is the appropriate treatment and laparoscopic approach presents itself as a minimally invasive alternative. Case report: Patient with late left diaphragmatic lesion diagnosed four years after penetrating trauma. As clinical signs presented strong left hypochondrial pain, and stop elimination of gases and faeces. He was submitted to videolaparoscopy, with a view of diaphragmatic hernia, reduction of herniated organs, suture of the diaphragmatic defect and thoracic drainage. Had an uneventful recovery and was discharged on the fourth postoperative day. Comments: post traumatic diaphragmatic hernia should be investigated in all patients with lesions in thoracoabdominal region. As can be asymptomatic, it is necessary systematic research to diagnosis, avoiding late complications associated with high morbidity and mortality rates
Hospital Variation in Functional Recovery After Stroke
Authors: Bettger Janet Prvu , Thomas Laine , Liang Li , Xian Ying , Bushnell Cheryl D. , Saver Jeffrey L. , Fonarow Gregg C. , Peterson Eric D.
Published: January 2017

Background—

Functional status is a key patient-centric outcome, but there are little data on whether functional recovery post-stroke varies among hospitals. This study examined the distribution of functional status 3 months after stroke, determined whether these outcomes vary among hospitals, and identified hospital characteristics associated with better (or worse) functional outcomes.

Methods and Results—

Observational analysis of the AVAIL study (Adherence Evaluation After Ischemic Stroke-Longitudinal) included 2083 ischemic stroke patients enrolled from 82 US hospitals participating in Get With The Guidelines-Stroke and AVAIL. The primary outcome was dependence or death at 3 months (modified Rankin Scale [mRS] score of 3–6). Secondary outcomes included functional dependence (mRS score of 3–5), disabled (mRS score of 2–5), and mRS evaluated as a continuous score. By 3 months post-discharge, 36.5% of patients were functionally dependent or dead. Rates of dependence or death varied widely by discharging hospitals (range: 0%–67%). After risk adjustment, patients had lower rates of 3-month dependence or death when treated at teaching hospitals (odds ratio, 0.72; 95% confidence interval, 0.54–0.96) and certified primary stroke centers (odds ratio, 0.69; 95% confidence interval, 0.53–0.91). In contrast, a composite measure of hospital-level adherence to acute stroke care performance metrics, stroke volume, and bed size was not associated with downstream patient functional status. Findings were robust across mRS end points and sensitivity analyses.

Conclusions—

One third of acute ischemic stroke patients were functionally dependent or dead 3 months postacute stroke; functional recovery rates varied considerably among hospitals, supporting the need to better determine which care processes can maximize functional outcomes.
Atrial Fibrillation Diagnosis Timing, Ambulatory ECG Monitoring Utilization, and Risk of Recurrent Stroke
Authors: Lip Gregory Y. H. , Hunter Tina D. , Quiroz Maria E. , Ziegler Paul D. , Turakhia Mintu P.
Published: January 2017

Background—

The risk of recurrence after an initial ischemic stroke or transient ischemic attack (TIA) may be impacted by undiagnosed atrial fibrillation (AF). We therefore assessed the impact of AF diagnosis and timing on stroke/TIA recurrence rates in a large real-world sample of patients.

Methods and Results—

Using commercial claims data (Truven Health Analytics MarketScan), we performed a retrospective cohort study of patients with an index stroke or TIA event recorded in years 2008 through 2011. Patients were characterized by baseline oral anticoagulation, CHADS
2
and CHA
2
DS
2
-VASc scores, AF diagnosis and timing with respect to the index stroke, and presence or absence of post-index ambulatory cardiac monitoring. The primary outcome was the recurrence of an ischemic stroke or TIA. Of 179 160 patients (age 67±16.2 years; 53.7% female), the Kaplan-Meier estimate for stroke/TIA recurrence within 1 year was 10.6%. Not having oral anticoagulation prescribed at baseline and having AF first diagnosed >7 days post-stroke (late AF) was highly associated with recurrent stroke/TIA (hazard ratio, 2.0; 95% confidence interval, 1.9–2.1). Among patients with at least 1 year of follow-up, only 2.6% and 9.7% had ambulatory ECG monitoring in the 7 days and 12 months post-stroke, respectively.

Conclusions—

AF diagnosed after stroke is an important hallmark of recurrent stroke risk. Increasing the low utilization of cardiac monitoring after stroke could identify undiagnosed AF earlier, leading to appropriate oral anticoagulation treatment and a reduction in stroke/TIA recurrence.
Racial and Ethnic Differences in Antihypertensive Medication Use and Blood Pressure Control Among US Adults With Hypertension
Authors: Gu Anna , Yue Yu , Desai Raj P. , Argulian Edgar
Published: January 2017

Background—

A key to reduce and eradicate racial disparities in hypertension outcomes is to understand their causes. We aimed at evaluating racial differences in antihypertensive drug utilization patterns and blood pressure control by insurance status, age, sex, and presence of comorbidities.

Methods and Results—

A total of 8796 hypertensive individuals ≥18 years of age were identified from the National Health and Nutrition Examination Survey (2003–2012) in a repeated cross-sectional study. During the study period, all 3 racial groups (whites, blacks, and Hispanics) experienced substantial increase in hypertension treatment and control. The overall treatment rates were 73.9% (95% confidence interval [CI], 71.6%–76.2%), 70.8% (95% CI, 68.6%–73.0%), and 60.7% (95% CI, 57.0%–64.3%) and hypertension control rates were 42.9% (95% CI, 40.5%–45.2%), 36.9% (95% CI, 34.7%–39.2%), and 31.2% (95% CI, 28.6%–33.9%) for whites, blacks, and Hispanics, respectively. When stratified by insurance status, blacks (odds ratio, 0.74 [95% CI, 0.64–0.86] for insured and 0.59 [95% CI, 0.36–0.94] for uninsured) and Hispanics (odds ratio, 0.74 [95% CI, 0.60–0.91] for insured and 0.58 [95% CI, 0.36–0.94] for uninsured) persistently had lower rates of hypertension control compared with whites. Racial disparities also persisted in subgroups stratified by age (≥60 and <60 years of age) and presence of comorbidities but worsened among patients <60 years of age.

Conclusions—

Black and Hispanic patients had poorer hypertension control compared with whites, and these differences were more pronounced in younger and uninsured patients. Although black patients received more intensive antihypertensive therapy, Hispanics were undertreated. Future studies should further explore all aspects of these disparities to improve cardiovascular outcomes.
Use of Strategies to Improve Door-to-Needle Times With Tissue-Type Plasminogen Activator in Acute Ischemic Stroke in Clinical Practice
Authors: Xian Ying , Xu Haolin , Lytle Barbara , Blevins Jason , Peterson Eric D. , Hernandez Adrian F. , Smith Eric E. , Saver Jeffrey L. , Messé Steven R. , Paulsen Mary , Suter Robert E. , Reeves Mathew J. , Jauch Edward C. , Schwamm Lee H. , Fonarow Gregg C.
Published: January 2017

Background—

The implementation of Target: Stroke Phase I, the first stage of the American Heart Association’s national quality improvement initiative to accelerate door-to-needle (DTN) times, was associated with an average 15-minute reduction in DTN times. Target: Stroke phase II was launched in April 2014 with a goal of promoting further reduction in treatment times for tissue-type plasminogen activator (tPA) administration.

Methods and Results—

We conducted a second survey of Get With The Guidelines-Stroke hospitals regarding strategies used to reduce delays after Target: Stroke and quantify their association with DTN times. A total of 16 901 ischemic stroke patients were treated with intravenous tPA within 4.5 hours of symptom onset from 888 surveyed hospitals between June 2014 and April 2015. The patient-level median DTN time was 56 minutes (interquartile range, 42–75), with 59.3% of patients receiving intravenous tPA within 60 minutes and 30.4% within 45 minutes after hospital arrival. Most hospitals reported routinely using a majority of Target: Stroke key practice strategies, although direct transport of patients to computed tomographic/magenetic resonance imaging scanner, premix of tPA ahead of time, initiation of tPA in brain imaging suite, and prompt data feedback to emergency medical services providers were used less frequently. Overall, we identified 16 strategies associated with significant reductions in DTN times. Combined, a total of 20 minutes (95% confidence intervals 15–25 minutes) could be saved if all strategies were implemented.

Conclusions—

Get With The Guidelines-Stroke hospitals have initiated a majority of Target: Stroke–recommended strategies to reduce DTN times in acute ischemic stroke. Nevertheless, certain strategies were infrequently practiced and represent a potential immediate target for further improvements.
Autologous Cell Therapy for Peripheral Arterial Disease
Authors: Rigato Mauro , Monami Matteo , Fadini Gian Paolo
Published: January 2017

Rationale:

Critical limb ischemia is a life-threatening complication of peripheral arterial disease. In patients who are ineligible for revascularization procedures, there are few therapeutic alternatives, leading to amputations and death.

Objective:

To provide a systematic review of the literature and a meta-analysis of studies evaluating safety and efficacy of autologous cell therapy for intractable peripheral arterial disease/critical limb ischemia.

Methods and Results:

We retrieved 19 randomized controlled trials (837 patients), 7 nonrandomized trials (338 patients), and 41 noncontrolled studies (1177 patients). The primary outcome was major amputation. Heterogeneity was high, and publication bias could not be excluded. Despite these limitations, the primary analysis (all randomized controlled trials) showed that cell therapy reduced the risk of amputation by 37%, improved amputation-free survival by 18%, and improved wound healing by 59%, without affecting mortality. Cell therapy significantly increased ankle brachial index, increased transcutaneous oxygen tension, and reduced rest pain. The secondary analysis (all controlled trials; n=1175 patients) shows that there may be potential to avoid ≈1 amputation/year for every 2 patients successfully treated. The tertiary analysis (all studies; n=2332 patients) precisely estimated the changes in ankle brachial index, transcutaneous oxygen tension, rest pain, and walking capacity after cell therapy. Intramuscular implantation appeared more effective than intra-arterial infusion, and mobilized peripheral blood mononuclear cells may outperform bone marrow–mononuclear cells and mesenchymal stem cells. Amputation rate was improved more in trials wherein the prevalence of diabetes mellitus was high. Cell therapy was not associated with severe adverse events. Remarkably, efficacy of cell therapy on all end points was no longer significant in placebo-controlled randomized controlled trials and disappeared in randomized controlled trials with a low risk of bias.

Conclusions:

Although this meta-analysis highlights the need for more high-quality placebo-controlled trials, equipoise may no longer be guaranteed because autologous cell therapy has the potential to modify the natural history of intractable critical limb ischemia.
High‐Saturated‐Fat Diet Increases Circulating Angiotensin‐Converting Enzyme, Which Is Enhanced by the rs4343 Polymorphism Defining Persons at Risk of Nutrient‐Dependent Increases of Blood Pressure
Authors: Schüler Rita , Osterhoff Martin A. , Frahnow Turid , Seltmann Anne‐Cathrin , Busjahn Andreas , Kabisch Stefan , Xu Li , Mosig Alexander S. , Spranger Joachim , Möhlig Matthias , Hornemann Silke , Kruse Michael , Pfeiffer Andreas F. H.
Published: January 2017

Background

Angiotensin‐converting enzyme (
ACE
) plays a major role in blood pressure regulation and cardiovascular homeostasis. Contrary to the assumption that
ACE
levels are stable, circulating
ACE
has been shown to be altered in obesity and weight loss. We sought to examine effects of a high‐saturated‐fat (
HF
) diet on
ACE
within the
NU
triGenomic Analysis in Twins (
NUGAT
) study.

Methods and Results

Forty‐six healthy and nonobese twin pairs initially consumed a carbohydrate‐rich, low‐fat diet over a period of 6 weeks to standardize for nutritional behavior prior to the study, followed by 6 weeks of
HF
diet under isocaloric conditions. After 6 weeks of
HF
diet, circulating
ACE
concentrations increased by 15% (
P
=1.6×10
−30
), accompanied by an increased
ACE
gene expression in adipose tissue (
P
=3.8×10
−6
). Stratification by
ACE
rs4343, a proxy for the
ACE
insertion/deletion polymorphism (I/D), revealed that homozygous carriers (
GG
) of the variant had higher baseline
ACE
concentrations (
P
=7.5×10
−8
) and additionally showed a 2‐fold increase in
ACE
concentrations in response to the
HF
diet as compared to non‐ or heterozygous carriers (
AA
/
AG
,
P
=2×10
−6
).
GG
carriers also responded with higher systolic blood pressure as compared to
AA
/
AG
carriers (
P=
0.008). The strong gene‐diet interaction was confirmed in a second independent, cross‐sectional cohort, the Metabolic Syndrome Berlin Potsdam (MeSyBePo) study.

Conclusions

The
HF
‐diet‐induced increase of
ACE
serum concentrations reveals
ACE
to be a potential molecular link between dietary fat intake and hypertension and cardiovascular disease (
CVD
). The
GG
genotype of the
ACE
rs4343 polymorphism represents a robust nutrigenetic marker for an unfavorable response to high‐saturated‐fat diets.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01631123.
Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial
Authors: Hu Peter T. , Lopes Renato D. , Stevens Susanna R. , Wallentin Lars , Thomas Laine , Alexander John H. , Hanna Michael , Lewis Basil S. , Verheugt Freek W. A. , Granger Christopher B. , Jones W. Schuyler
Published: January 2017

Background

We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (
PAD
) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without
PAD
.

Methods and Results

The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had
PAD
at baseline. Patients with
PAD
had higher unadjusted rates of stroke and systemic embolism (hazard ratio [
HR
] 1.73, 95%
CI
1.22–2.45;
P
=0.002) and major bleeding (
HR
1.34, 95%
CI
1.00–1.81;
P
=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (
HR
1.32, 95%
CI
0.93–1.88;
P
=0.12) and major bleeding (
HR
1.03, 95%
CI
0.76–1.40;
P
=0.83) compared with patients without
PAD
. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with
PAD
(
HR
0.63, 95%
CI
0.32–1.25) and without
PAD
(
HR
0.80, 95%
CI
0.66–0.96; interaction
P
=0.52). Patients with
PAD
did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (
HR
1.05, 95%
CI
0.69–1.58), whereas those without
PAD
had a statistically significant reduction (
HR
0.65, 95%
CI
0.58–0.73; interaction
P
=0.03).

Conclusions

Patients with
PAD
in
ARISTOTLE
had a higher crude risk of stroke or systemic embolism compared with patients without
PAD
that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without
PAD
. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and
PAD
.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00412984.
Finger Tracking Reveals the Covert Stages of Mental Arithmetic
Authors: Pinheiro-Chagas Pedro , Dotan Dror , Piazza Manuela , Dehaene Stanislas
Published: January 2017

We introduce a novel method capable of dissecting the succession of processing stages underlying mental arithmetic, thus revealing how two numbers are transformed into a third. We asked adults to point to the result of single-digit additions and subtractions on a number line, while their finger trajectory was constantly monitored. We found that the two operands are processed serially: the finger first points toward the larger operand, then slowly veers toward the correct result. This slow deviation unfolds proportionally to the size of the smaller operand, in both additions and subtractions. We also observed a transient operator effect: a plus sign attracted the finger to the right and a minus sign to the left and a transient activation of the absolute value of the subtrahend. These findings support a model whereby addition and subtraction are computed by a stepwise displacement on the mental number line, starting with the larger number and incrementally adding or subtracting the smaller number.
The Cognitive Boundaries of Responsibility (Die kognitiven Grenzen der Verantwortung)
Authors: Weichold Martin
Published: January 2017

This paper poses a new challenge to control-based theories of moral responsibility. Control-based theories – as defended, for instance, by Aristotle and John Martin Fischer – hold that an agent is responsible for an action only if she acted voluntarily and knew what she was doing. However, this paper argues that there is a large class of cases of unreflective behavior of which the following is true: (a) the persons involved did not have the kind of control required by control-based theories, yet (b) we intuitively take the persons involved to be morally responsible.
Two new species of Eriope (Lamiaceae) from Goiás state, Brazil
Authors: SCHLIEWE MARCOS AUGUSTO , FERREIRA HELENO DIAS , REZENDE MARIA HELENA , GRACIANO-RIBEIRO DALVA
Published: January 2017

Eriope harleyi and E. paradise, two new plant species from central Brazil, are described and illustrated. Eriope harleyi is similar to E. crassipes, but differs in the presence of ovate or orbicular leaves, leaf size (1.8–2.5 × 1.2–1.8 cm), length of petiole (0.15–0.35 cm), presence of bracteoles in the pseudopedicel base and marginal vein fimbriate in E. harleyi (versus lanceolate-elliptic leaf, leaf size (4.0–7.5 × 1.5–3.5 cm), length of petiole (0.50–1.50 cm), and the absence of bracteoles in the pseudopedicel base and marginal vein in arches). Eriope paradise is similar to E. complicata but this new species does not have prominent tertiary veins on its abaxial surface nor bracteoles in the pseudopedicel base, and has inflorescences forming a monothyrse (versus prominent tertiary veins in abaxial face, presence of bracteoles in pseudopedicel base and inflorescence in diplothyrse). Presence of a hypoderm, stomata on both faces of the leaf epidermis, and straight or sinuous contour of the anticlinal walls of leaf epidermal cells are all examples of characteristics of leaf anatomy used for the establishment of this new taxa. Data about the habitat, phenology, conservation status, and geographic location are also presented.
Pleione arunachalensis (Orchidaceae: Epidendroideae: Arethuseae: Coelogyninae), a new species from North-East India
Authors: HAREESH VADAKKOOT SANKARAN , KUMAR PANKAJ , SABU MAMIYIL
Published: January 2017

Pleione arunachalensis, a new species is described from Lower Dibang Valley district of Arunachal Pradesh, North-East India. Detailed descriptions, distribution, ecology, colour photographs and key to identification for Indian Pleione is provided.
Checklist of Cerambycidae (Coleoptera) primary types of the Coleção Entomológica Pe. Jesus Santiago Moure, Departamento de Zoologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil, Instituto Nacional de Pesquisas da Amazônia, Amazonas, Manaus, Brazil, and of the Museu Paraense Emílio Goeldi, Pará, Belém, Brazil
Authors: MONNÉ MIGUEL A. , ALMEIDA LUCIA M. , OLIVEIRA MARCIO L. , VIANA JÉSSICA HERZOG , MONNÉ MARCELA L.
Published: January 2017

The primary types of Cerambycidae (Coleoptera) deposited in the Coleção Entomológica Pe. Jesus Santiago Moure, Departamento de Zoologia, Universidade Federal do Paraná, Curitiba, Paraná, Brazil (DZUP), Instituto Nacional de Pesquisas da Amazônia, Amazonas, Manaus, Brazil (INPA), and in the Museu Paraense Emílio Goeldi, Pará, Belém,Brazil (MPEG) are catalogued. There are 54 primary types of Cerambycidae in the DZUP, 48 in the INPA, and 25 in the MPEG.
Description of a new species of the genus Tophoderes Dejean (Coleoptera: Anthribidae) from east Madagascar, with images of all Madagascan species of the genus
Authors: TRÝZNA MILOŠ
Published: January 2017

A new species Tophoderes banari Trýzna sp. nov. (Anthribidae: Anthribinae: Tophoderini) from east Madagascar is described. Both sexes and male and female genitalia are illustrated. Colour photographs of all Madagascan species of the genus Tophoderes are added.
Characterization of Heat Waves in the Sahel and Associated Physical Mechanisms
Authors: Oueslati Boutheina , Pohl Benjamin , Moron Vincent , Rome Sandra , Janicot Serge
Published: January 2017

Great effort is made to address heat waves (HWs) in developed countries because of their devastating impacts on society, economy, and environment. However, HWs are still understudied over developing countries. This is particularly true in West Africa, and especially in the Sahel, where temperatures recurrently reach critical values, such as during the 2010 HW event in the western Sahel. This work aims at characterizing the Sahelian HWs during boreal spring seasons (April–May–June) and understanding the mechanisms associated with such extreme events. Over the last three decades, Sahelian HWs have been becoming more frequent, lasting longer, covering larger areas, and reaching higher intensities. The physical mechanisms associated with HWs are examined to assess the respective roles of atmospheric dynamics and radiative and turbulent fluxes by analyzing the surface energy budget. Results suggest that the greenhouse effect of water vapor is the main driver of HWs in the western Sahel, increasing minimum temperatures by enhanced downward longwave radiation. Atmospheric circulation plays an important role in sustaining these warm anomalies by advecting moisture from the Atlantic Ocean and the Guinean coasts into the Sahel. Maximum temperature anomalies are mostly explained by increased downward shortwave radiation due to a reduction in cloud cover. Interannual variability of HWs is affected by the delayed impact of El Niño–Southern Oscillation (ENSO), with anomalous temperature warming following warm ENSO events, resulting from an amplified water vapor feedback.
Precipitation Associated with Convergence Lines
Authors: Weller Evan , Shelton Kay , Reeder Michael J. , Jakob Christian
Published: January 2017

Precipitation is often organized along coherent lines of low-level convergence, which at longer time and space scales form well-known convergence zones over the world’s oceans. Here, an automated, objective method is used to identify instantaneous low-level convergence lines in reanalysis data and calculate their frequency for the period 1979–2013. Identified convergence lines are combined with precipitation observations to assess the extent to which precipitation around the globe is associated with convergence lines in the lower troposphere. It is shown that a large percentage of precipitation (between 65% and 90%) over the tropical oceans is associated with such convergence lines, with large regional variations of up to 30% throughout the year, especially in the eastern Pacific and Atlantic Oceans. Over land, the annual-mean proportion of precipitation associated with convergence lines ranges between 30% and 60%, and the lowest proportions (less than 15%) associated with convergence lines occur on the eastern flank of the subtropical highs. Overall, much greater precipitation is associated with long coherent lines (greater than 300 km in length) than with shorter fragmented lines (less than 300 km), and the majority of precipitation associated with shorter lines occurs over land. The proportion of precipitation not associated with any convergence line primarily occurs where both precipitation and frequency of convergence lines are low. The high temporal and spatial resolution of the climatology constructed also enables an examination of the diurnal cycle in the relationship between convergence lines and precipitation. Here an example is provided over the tropical Maritime Continent region.
Comparisons of Global Terrestrial Surface Water Datasets over 15 Years
Authors: Pham-Duc Binh , Prigent Catherine , Aires Filipe , Papa Fabrice
Published: January 2017

Continental surface water extents and dynamics are key information to model Earth’s hydrological and biochemical cycles. This study presents global and regional comparisons between two multisatellite surface water extent datasets, the Global Inundation Extent from Multi-Satellites (GIEMS) and the Surface Water Microwave Product Series (SWAMPS), for the 1993–2007 period, along with two widely used static inundation datasets, the Global Lakes and Wetlands Database (GLWD) and the Matthews and Fung wetland estimates. Maximum surface water extents derived from these datasets are largely different: ~13 × 106 km2 from GLWD, ~5.3 × 106 km2 from Matthews and Fung, ~6.2 × 106 km2 from GIEMS, and ~10.3 × 106 km2 from SWAMPS. SWAMPS global maximum surface extent reduces by nearly 51% (to ~5 × 106 km2) when applying a coastal filter, showing a strong contamination in this retrieval over the coastal regions. Anomalous surface waters are also detected with SWAMPS over desert areas. The seasonal amplitude of the GIEMS surface waters is much larger than the SWAMPS estimates, and GIEMS dynamics is more consistent with other hydrological variables such as the river discharge. Over the Amazon basin, GIEMS and SWAMPS show a very high time series correlation (95%), but with SWAMPS maximum extent half the size of that from GIEMS and from previous synthetic aperture radar estimates. Over the Niger basin, SWAMPS seasonal cycle is out of phase with both GIEMS and MODIS-derived water extent estimates, as well as with river discharge data.
Nordic Impact: Article Productivity and Citation Patterns in Sixteen Nordic Sociology Departments
Authors: Bjarnason Thoroddur , Sigfusdottir Inga Dora
Published: January 2017

The sociology departments in the Nordic countries provide the institutional platform for Nordic Sociology and for the Nordic national sociological associations that form the Scandinavian Sociological Association. This paper focuses on journal articles produced by current (as of 1 January 2001) faculty of 16 of these Nordic Sociology departments in the period 1981-2000. First, we provide a brief overview of article productivity and citations to articles produced in this period by country and department. Second, we estimate a multilevel model of citation patterns by articles published, the academic position and productivity of each author, and the structure and productivity of each department as a whole. Third, we test the extent to which the effects of such factors differ between departments and individuals. In all departments, publications in high-impact journals increase the number of citations to any given article, to other work of the same author, and to the work of other faculty in the department. The effect of publishing in high-impact journals differs significantly between individual authors, and work in certain types of journals yields more citations than the journal impact factor would predict. We argue that departmental affiliations with outside faculty and departmental productivity can be seen as a form of social capital that benefits both individuals and departments as a whole. These findings strongly suggest that diversity is a defining characteristic of this sociological community, precluding monolithic definitions of Nordic sociology.
Do Norms Count? State Regulation and Compliance in a Norwegian Fishing Community
Authors: Gezelius Stig S.
Published: January 2017

This article addresses the interface between law and the morality of civil society. It starts with a review of the discourse between the utilitarian approach to rationality and perspectives which include normative action. It subsequently explores the dynamics of compliance and noncompliance among a group of Norwegian fishermen. The choice of compliance was guided by an informally enforced set of moral norms, which largely dissolved the connection between expected benefit and the likeliness of infractions. This moral system defined instances in which violations could take place without being met with informal sanctions, and thus also allowed for strategic action to some extent. The article illustrates how civil society enforces the law according to moral rather than legal standards, and it ends with a suggested concept of legitimacy of law.
KSR and the Supreme Court: The Silence is Deafening
Authors: Jones Paul
Published: January 2017

One of the uses of history is to free us of a falsely imagined past. The less we know of how ideas actually took root and grew, the more apt we are to accept them unquestioningly, as inevitable features of the world in which we move. One reason for the stifling solidity of received opinion about antitrust, why counterargument makes so little headway, is that most of us accept our first principles and even our immediate premises uncritically, as given, because we assume that they were established theoretically and confirmed empirically by legislators and judges long ago.

If awareness of anomaly plays a role in the emergence of new sorts of phenomena, it should surprise no one that a similar but more profound awareness is prerequisite to all acceptable changes of theory.