bluuebunny/crossref_metadata_2025 huggingface dataset:
Go-activation endures following the presentation of a stop-signal: evidence from startle
Authors: Drummond Neil M. , Cressman Erin K. , Carlsen Anthony N.
Published: November 2016

It has been proposed that, in a stop-signal task (SST), independent go- and stop-processes “race” to control behavior. If the go-process wins, an overt response is produced, whereas, if the stop-process wins, the response is withheld. One prediction that follows from this proposal is that, if the activation associated with one process is enhanced, it is more likely to win the race. We looked to determine whether these initiation and inhibition processes (and thus response outcomes) could be manipulated by using a startling acoustic stimulus (SAS), which has been shown to provide additional response activation. In the present study, participants were to respond to a visual go-stimulus; however, if a subsequent stop-signal appeared, they were to inhibit the response. The stop-signal was presented at a delay corresponding to a probability of responding of 0.4 (determined from a baseline block of trials). On stop-trials, a SAS was presented either simultaneously with the go-signal or stop-signal or 100, 150, or 200 ms following the stop-signal. Results showed that presenting a SAS during stop-trials led to an increase in probability of responding when presented with or following the stop-signal. The latency of SAS responses at the stop-signal + 150 ms and stop-signal + 200 ms probe times suggests that they would have been voluntarily inhibited but instead were involuntarily initiated by the SAS. Thus results demonstrate that go-activation endures even 200 ms following a stop-signal and remains accessible well after the response has been inhibited, providing evidence against a winner-take-all race between independent go- and stop-processes.

NEW & NOTEWORTHY In this study, a startling acoustic stimulus (SAS) was used to determine whether response outcome could be manipulated in a stop-signal task. Results revealed that presenting a SAS during stop-signal trials led to an increase in probability of responding even when presented 200 ms following the stop-signal. The latency of SAS responses indicates that go-activation remains accessible and modifiable well after the response is voluntarily inhibited, providing evidence against an irrevocable commitment to inhibition.
Contrast sensitivity, V1 neural activity, and natural vision
Authors: Niemeyer James E. , Paradiso Michael A.
Published: November 2016

Contrast sensitivity is fundamental to natural visual processing and an important tool for characterizing both visual function and clinical disorders. We simultaneously measured contrast sensitivity and neural contrast response functions and compared measurements in common laboratory conditions with naturalistic conditions. In typical experiments, a subject holds fixation and a stimulus is flashed on, whereas in natural vision, saccades bring stimuli into view. Motivated by our previous V1 findings, we tested the hypothesis that perceptual contrast sensitivity is lower in natural vision and that this effect is associated with corresponding changes in V1 activity. We found that contrast sensitivity and V1 activity are correlated and that the relationship is similar in laboratory and naturalistic paradigms. However, in the more natural situation, contrast sensitivity is reduced up to 25% compared with that in a standard fixation paradigm, particularly at lower spatial frequencies, and this effect correlates with significant reductions in V1 responses. Our data suggest that these reductions in natural vision result from fast adaptation on one fixation that lowers the response on a subsequent fixation. This is the first demonstration of rapid, natural-image adaptation that carries across saccades, a process that appears to constantly influence visual sensitivity in natural vision.

NEW & NOTEWORTHY Visual sensitivity and activity in brain area V1 were studied in a paradigm that included saccadic eye movements and natural visual input. V1 responses and contrast sensitivity were significantly reduced compared with results in common laboratory paradigms. The parallel neural and perceptual effects of eye movements and stimulus complexity appear to be due to a form of rapid adaptation that carries across saccades.
A Pareto-Based Adaptive Variable Neighborhood Search for Biobjective Hybrid Flow Shop Scheduling Problem with Sequence-Dependent Setup Time
Authors: Tian Huixin , Li Kun , Liu Wei
Published: November 2016

Different from most researches focused on the single objective hybrid flowshop scheduling (HFS) problem, this paper investigates a biobjective HFS problem with sequence dependent setup time. The two objectives are the minimization of total weighted tardiness and the total setup time. To efficiently solve this problem, a Pareto-based adaptive biobjective variable neighborhood search (PABOVNS) is developed. In the proposed PABOVNS, a solution is denoted as a sequence of all jobs and a decoding procedure is presented to obtain the corresponding complete schedule. In addition, the proposed PABOVNS has three major features that can guarantee a good balance of exploration and exploitation. First, an adaptive selection strategy of neighborhoods is proposed to automatically select the most promising neighborhood instead of the sequential selection strategy of canonical VNS. Second, a two phase multiobjective local search based on neighborhood search and path relinking is designed for each selected neighborhood. Third, an external archive with diversity maintenance is adopted to store the nondominated solutions and at the same time provide initial solutions for the local search. Computational results based on randomly generated instances show that the PABOVNS is efficient and even superior to some other powerful multiobjective algorithms in the literature.
Clinical Outcome of a Novel Anti-CD6 Biologic Itolizumab in Patients of Psoriasis with Comorbid Conditions
Authors: Singh Vinay
Published: November 2016

Psoriasis is a common, chronic, immune mediated, inflammatory disease of skin characterized by red patches enclosed with white scales and affects 2-3% of people in the world. Topical therapy, phototherapy, and systemic therapy were employed for management of disease from many last decades. However, long term uses of these agents are associated with unwanted effects and toxicities. Recently, Itolizumab has been developed as world’s first anti-CD6 humanized monoclonal IgG1 antibody for the management of moderate-to-severe chronic plaque psoriasis in India. Here we are presenting the response indicated by Itolizumab in 7 Indian patients having moderate-to-severe psoriasis with severe comorbidities and who were intolerant/nonresponding to conventional therapies.
Forskolin Inhibits Lipopolysaccharide-Induced Modulation of MCP-1 and GPR120 in 3T3-L1 Adipocytes through an Inhibition of NFκB
Authors: Chiadak Jeanne Durendale , Arsenijevic Tatjana , Verstrepen Kevin , Gregoire Françoise , Bolaky Nargis , Delforge Valérie , Flamand Véronique , Perret Jason , Delporte Christine
Published: November 2016

In an obese state, Toll-like receptor-4 (TLR-4) upregulates proinflammatory adipokines secretion including monocyte chemotactic protein-1 (MCP-1) in adipose tissue. In contrast, G-protein coupled receptor 120 (GPR120) mediates antiobesity effects. The aim of this study was to determine the signaling pathway by which Forskolin (FK), a cyclic adenosine monophosphate- (cAMP-) promoting agent causing positive changes in body composition in overweight and obese adult men, affects MCP-1 and GPR120 expression during an inflammatory response induced by lipopolysaccharide (LPS) in adipocytes, such as in an obese state. 3T3-L1 cells differentiated into adipocytes (DC) were stimulated with LPS in the absence or presence of FK and inhibitors of TLR-4 and inhibitor of kappa B (IκBα). In DC, LPS increased MCP-1, TLR-4, and nuclear factor-κB1 (NFκB1) mRNA levels, whereas it decreased GPR120 mRNA levels. In DC, FK inhibited the LPS-induced increase in MCP-1, TLR-4, and NFκB1 mRNA levels and the LPS-induced decrease in GPR120 mRNA. BAY11-7082 and CLI-095 abolished these LPS-induced effects. In conclusion, FK inhibits LPS-induced increase in MCP-1 mRNA levels and decrease in GPR120 mRNA levels in adipocytes and may be a potential treatment for inflammation in obesity. Furthermore, TLR-4-induced activation of NFκB may be involved in the LPS-induced regulation of these genes.
Evaluation of Peripapillary Nerve Fiber Layer after Dexamethasone Implantation (Ozurdex) in Branch Retinal Vein Occlusions
Authors: Bulut Muhammed Nurullah , Özertürk Yusuf , Çallı Ümit , Akçay Güzide , Kıvrak Ulviye , Bulut Kezban
Published: November 2016

Purpose. To evaluate the peripapillary retinal nerve fiber layer (RNFL) thicknesses of patients treated with intravitreal Ozurdex implant due to branch retinal vein occlusion (BRVO) related macular edema (ME). Methods. Thirty-three eyes of 33 patients treated with Ozurdex implant due to ME associated with BRVO were included in the study. Ophthalmic examinations including determination of best corrected visual acuity (BCVA), measurement of intraocular pressure (IOP), and central macular thickness (CMT) and peripapillary RNFL assessment with optical coherence tomography (OCT) were performed before the injection of Ozurdex implant and during the 6-month follow-up period after the injection. Results. The mean age was 55.2 ± 7.4 (range: 40–68) years. The BCVAs were significantly increased and CMTs were significantly decreased at month 3 and month 6 visits compared to baseline values. The mean IOP was significantly increased from baseline at day 1, week 1, and month 1 visits (p1=0.008, p2=0.018, and p3=0.022, resp.). The average and inferior quadrant peripapillary RNFL thicknesses were significantly reduced at month 6 control visit compared to baseline values (both p<0.001). Conclusions. Ozurdex implant improved the BCVA and reduced the CMT in the eyes with RVO related ME. However, IOP elevations occurred within the first month after the injection and the average and inferior quadrant RNFL thinning was found six months after the injection. Further controlled studies are warranted.
Risk of Cancer among Commercially Insured HIV-Infected Adults on Antiretroviral Therapy
Authors: Lee Jeannette Y. , Dhakal Ishwori , Casper Corey , Noy Ariela , Palefsky Joel M. , Haigentz Missak , Krown Susan E. , Ambinder Richard F. , Mitsuyasu Ronald T.
Published: November 2016

The objective of this study was to explore the cancer incidence rates among HIV-infected persons with commercial insurance who were on antiretroviral therapy and compare them with those rates in the general population. Paid health insurance claims for 63,221 individuals 18 years or older, with at least one claim with a diagnostic code for HIV and at least one filled prescription for an antiretroviral medication between January 1, 2006, and September 30, 2012, were obtained from the LifeLink® Health Plan Claims Database. The expected number of cancer cases in the general population for each gender-age group (<30, 30–39, 40–49, 50–59, and >60 years) was estimated using incidence rates from the Surveillance Epidemiology and End Results (SEER) program. Standardized incidence ratios (SIRs) were estimated using their 95% confidence intervals (CIs). Compared to the general population, incidence rates for HIV-infected adults were elevated (SIR, 95% CI) for Kaposi sarcoma (46.08; 38.74–48.94), non-Hodgkin lymphoma (4.22; 3.63–4.45), Hodgkin lymphoma (9.83; 7.45–10.84), and anal cancer (30.54; 25.62–32.46) and lower for colorectal cancer (0.69; 0.52–0.76), lung cancer (0.70; 0.54, 0.77), and prostate cancer (0.54; 0.45–0.58). Commercially insured, treated HIV-infected adults had elevated rates for infection-related cancers, but not for common non-AIDS defining cancers.
Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative Renal Dysfunction
Authors: Qi Yu , Uchida Tokujiro , Yamamoto Mamoru , Yamamoto Yudai , Kido Koji , Ito Hiroyuki , Ohno Nagara , Asahara Miho , Yamada Yoshitsugu , Yamaguchi Osamu , Mitaka Chieko , Tomita Makoto , Makita Koshi
Published: November 2016

Background. This study aimed to determine the perioperative change in serum double-strand DNA (dsDNA) as a marker potentially reflecting neutrophil extracellular trap concentration in samples from patients undergoing cardiac surgery and to analyze a relationship between serum dsDNA concentrations and perioperative renal dysfunction. Methods. Serum dsDNA concentrations in samples that were collected during a previously conducted, prospective, multicenter, observational study were measured. Eighty patients undergoing elective cardiac surgery were studied. Serum samples were collected at baseline, immediately after surgery, and the day after surgery (POD-1). Results. Serum dsDNA concentration was significantly increased from baseline (median, 398 ng/mL [interquartile range, 372–475 ng/mL]) to immediately after surgery (median, 540 ng/mL [437–682 ng/mL], p<0.001), and they were reduced by POD-1 (median, 323 ng/mL [256–436 ng/mL]). The difference in serum creatinine concentration between baseline and POD-1 was correlated with dsDNA concentration on POD-1 (rs=0.61, p<0.001). Conclusions. In patients undergoing cardiac surgery, serum dsDNA concentration is elevated postoperatively. Prolonged elevation in dsDNA concentration is correlated with perioperative renal dysfunction. Further large-scale studies are needed to determine the relationship between serum concentration of circulating dsDNA and perioperative renal dysfunction.
Numerical Simulations of the South American Low Level Jet in Two Episodes of MCSs: Sensitivity to PBL and Convective Parameterization Schemes
Authors: Santos Daniel Caetano , Nascimento Ernani de Lima
Published: November 2016

The sensitivity of numerical simulations of the low level jet stream (LLJS) in South America to the choice of parameterization schemes for the planetary boundary layer (PBL) and for cumulus convection using the Advanced Research core of the Weather Research and Forecast (WRF) model was assessed for two cases in which the development of Mesoscale Convective Systems (MCSs) was observed in the La Plata Basin at the exit of the LLJS. The MCSs developed under distinct synoptic forcing. Overall, the general area over the La Plata Basin where the wind profiles met LLJS criteria was larger in the situation with stronger frontal forcing. Regarding the impact of the choice of the PBL parameterization scheme upon the simulated LLJS, the nonlocal Yonsei University (YSU) scheme displayed slightly better results for most simulations regardless of the cumulus parameterization scheme utilized. In fact, the characterization of the LLJS in the simulations exhibited no significant sensitivity to the choice of the cumulus parameterization. In situations under stronger [weaker] frontal forcing, less [more] dispersion among the simulations was found regarding the identification of the LLJS.
The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood
Authors: Ferri Priscila Menezes , Simões e Silva Ana Cristina , Campos Silva Soraya Luiza , Aquino Diego Junior Queiroga de , Fagundes Eleonora Druve Tavares , Marques de Miranda Débora , Ferreira Alexandre Rodrigues
Published: November 2016

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.
Modelling and Automated Implementation of Optimal Power Saving Strategies in Coarse-Grained Reconfigurable Architectures
Authors: Palumbo Francesca , Fanni Tiziana , Sau Carlo , Meloni Paolo , Raffo Luigi
Published: November 2016

This paper focuses on how to efficiently reduce power consumption in coarse-grained reconfigurable designs, to allow their effective adoption in heterogeneous architectures supporting and accelerating complex and highly variable multifunctional applications. We propose a design flow for this kind of architectures that, besides their automatic customization, is also capable of determining their optimal power management support. Power and clock gating implementation costs are estimated in advance, before their physical implementation, on the basis of the functional, technological, and architectural parameters of the baseline design. Experimental results, on 90 and 45 nm CMOS technologies, demonstrate that the proposed approach guides the designer towards optimal implementation.
Thyroid Stimulating Hormone Is Increased in Hypertensive Patients with Obstructive Sleep Apnea
Authors: Li Nanfang , Heizhati Mulalibieke , Sun Chao , Abulikemu Suofeiya , Shao Liang , Yao Xiaoguang , Wang Yingchun , Hong Jing , Zhou Ling , Wang Lei , Zhang Yu , Zhang Weiwei
Published: November 2016

Purpose. To evaluate alteration in serum TSH in hypertensives with OSA and its relation with cardiometabolic risk factors. Methods. 517 hypertensives were cross-sectionally studied. OSA was determined by polysomnography and thyroid function by standard methods. Results. OSA was diagnosed in 373 hypertensives (72.15%). Prevalence of subclinical hypothyroidism was significantly higher in OSA hypertensives than in non-OSA ones (15.0% versus 6.9%, P=0.014). Serum LnTSH in hypertensives with severe OSA was significantly higher (0.99±0.81 versus 0.74±0.77 μIU/mL, P<0.05) than in those without OSA. AHI, LSaO2, ODI3, and ODI4 were independently associated with serum TSH for those aged 30–65 years. Dividing subjects into four groups as TSH < 1.0 μIU/mL, 1.0 ≤ THS ≤ 1.9 μIU/mL, 1.91 ≤ TSH < 4.5 μIU/mL, and TSH ≥ 4.5 μIU/mL, only 26.3% of OSA subjects exhibited TSH between 1.0 and 1.9 μIU/mL, significantly less than non-OSA subjects (26.3% versus 38.2%, P=0.01). DBP and serum LDL-c elevated with TSH increasing and were only significantly higher in TSH ≥ 4.5 μIU/mL group than in 1.0 ≤ TSH ≤ 1.9 μIU/mL group (96.32±14.19 versus 92.31±12.86 mmHg; P=0.040; 0.99±0.60 versus 0.87±0.34 mmol/L, P=0.023). Conclusion. OSA might be a risk factor for increased TSH even within reference range in hypertensive population.
Glycated Hemoglobin Levels in Patients with Decompensated Cirrhosis
Authors: Nadelson Jeffrey , Satapathy Sanjaya K. , Nair Satheesh
Published: November 2016

Introduction. Aim of this study is to determine if HbA1c levels are a reliable predictor of glycemic control in patients with decompensated cirrhosis.Methods. 200 unique patients referred for liver transplantation at University of Tennessee/Methodist University Transplant Institute with a HbA1c result were included. Three glucose levels prior to the “measured” A1c (MA1c) were input into an HbA1c calculator from the American Diabetes Association website to determine the “calculated” A1c (CA1c). The differences between MA1c and CA1c levels were computed. Patients were divided into three groups: group A, difference of <0.5; group B, 0.51–1.5; and group C, >1.5.Results. 97 (49%) patients had hemoglobin A1c of less than 5%. Discordance between calculated and measured HbA1c of >0.5% was seen in 47% (n=94). Higher level of discordance of greater than >1.5 was in 12% of patients (n=24). Hemoglobin was an independent predictor for higher discordance (odds ratio 0.77 95%, CI 0.60–0.99, andpvalue 0.04). HbA1c was an independent predictor of occurrence of HCC (OR 2.69 955, CI 1.38–5.43, andpvalue 0.008).Conclusion. HbA1c is not a reliable predictor of glycemic control in patients with decompensated cirrhosis, especially in those with severe anemia.
Stable Dispersed MoS2 Nanosheets in Liquid Lubricant with Enhanced Rate of Penetration for Directional Well
Authors: Lu Fuwei , Du Hui , Chen Zhaojun , Zhang Xianbin , Gong Houping , Xue Yun
Published: November 2016

MoS2 nanosheets of approx. 100 nm were synthesized by a reverse microemulsion route firstly, then were annealed under nitrogen atmosphere, and were finally modified with 1-dodecanethiol. The prepared MoS2 nanosheets were characterized by XRD, TEM, FTIR, and so forth. Experimental results show that MoS2 nanosheets with the typical layer structure can be easily dispersed in oil lubricant for rate of penetration (ROP) increasing in directional well. The ROP of directional well with the prepared liquid lubricant was 52.9% higher than that of the similar directional wells at least, and the drilling velocity was increased 20% while the total proportion of lubricant in drilling fluid was 1.5%.
Preclinical Evaluation of Chimeric Antigen Receptors Targeting CD70-Expressing Cancers
Authors: Wang Qiong J. , Yu Zhiya , Hanada Ken-ichi , Patel Krishna , Kleiner David , Restifo Nicholas P. , Yang James C.
Published: November 2016

Purpose: CD70 expression in normal tissues is restricted to activated lymphoid tissues. Targeting CD70 on CD70-expressing tumors could mediate “on-target, off-tumor” toxicity. This study was to evaluate the feasibility and safety of using anti-human CD70 CARs to treat cancer patients whose tumors express CD70.

Experimental Design: Seven anti-human CD70 CARs with binding moieties from human CD27 combined with CD3-zeta and different costimulatory domains from CD28 and/or 41BB were constructed. In vitro functionality of these receptors was compared and in vivo treatment efficacy was evaluated in a xenograft mouse model. A homologous, all murine anti-CD70 CAR model was also used to assess treatment-related toxicities.

Results: The CAR consisting of the extracellular binding portion of CD27 fused with 41BB and CD3-zeta (trCD27-41BB-zeta) conferred the highest IFNγ production against CD70-expressing tumors in vitro, and NSG mice bearing established CD70-expressing human tumors could be cured by human lymphocytes transduced with this CAR. In the murine CD27-CD3-zeta CAR model, significant reduction of established tumors and prolonged survival were achieved using CAR-transduced splenocytes in a dose-dependent manner. Host preirradiation enhanced treatment efficacy but increased treatment-related toxicities such as transient weight loss and hematopoetic suppression. The treatment did not appear to block adaptive host immune responses.

Conclusions: Preclinical testing supports the safety and efficacy of a CD27-containing CAR targeting CD70-expressing tumors. Clin Cancer Res; 23(9); 2267–76. ©2016 AACR.
TERT Promoter Mutations Enhance Telomerase Activation by Long-Range Chromatin Interactions
Authors: Min Jaewon , Shay Jerry W.
Published: November 2016

Summary: Although single-nucleotide somatic mutations in the proximal promoter of the human telomerase reverse transcriptase (TERT) gene create novel consensus sequences for transcription factors that enhance TERT expression, the precise mechanism of how telomerase is reactivated in cancer cells remains poorly understood. In this issue, Akıncılar and colleagues identify a potential mechanism of TERT reactivation that is mediated by a novel long-range chromatin interaction between the TERT promoter on chromosome 5p and a 300-kb upstream region. This permits recruitment of the transcription factor GABPA in mutant TERT promoters but not in wild-type promoters. Cancer Discov; 6(11); 1212–4. ©2016 AACR.

See related article by Akıncılar and colleagues, p. 1276.
Rescue of Tolerant CD8+ T Cells during Cancer Immunotherapy with IL2:Antibody Complexes
Authors: Klevorn Lauryn E. , Berrien-Elliott Melissa M. , Yuan Jinyun , Kuehm Lindsey M. , Felock Gregory D. , Crowe Sean A. , Teague Ryan M.
Published: November 2016

Interleukin-2 (IL2) was among the earliest reagents used for cancer immunotherapy due to its ability to support the survival and function of tumor-reactive T cells. However, treatment with IL2 is accompanied by off-target toxicity and low response rates in patients. In mouse models, these issues are largely overcome when IL2 is administered as a cytokine/antibody complex (IL2c). The complex has a longer serum half-life and can be designed for preferential cytokine delivery to specific cells of interest. Early studies showed IL2c could boost antitumor immunity in mice by activating tumor-reactive CD8+ T cells. But such functional T cells are often limited in the tumor microenvironment, where instead unresponsive tolerant T cells are eventually eliminated by apoptosis, representing a major obstacle to the success of cancer immunotherapy. We found that IL2c treatment rescued tumor-specific CD8+ T cells from a state of established tolerance, providing effective immunotherapy in tumor-bearing mice. Expression of the transcription factor T-bet was necessary to drive intratumoral IFNγ production and effector activity by T cells rescued with IL2c. Furthermore, IL2c promoted T-bet expression in human CD4+ and CD8+ T cells in humanized tumor-bearing mice, but also increased the frequency of Foxp3+ regulatory T cells. Our study reveals a novel role for IL2c as a powerful immunotherapeutic reagent capable of reversing tolerance in tumor-reactive T cells, and provides the first evidence that IL2c influences human T cells in vivo, highlighting the translational potential to modulate human antitumor immune responses. Cancer Immunol Res; 4(12); 1016–26. ©2016 AACR.
The Epidemiology of Cognitive Impairment in the Aging Population: Implications for Hearing Loss
Authors: Peracino Andrea , Pecorelli Sergio
Published: November 2016

Cognitive impairment and dementia are characterized by a progressive and devastating reduction in most cognitive abilities, functional independence, and social relationships. Dementia represents a substantial financial burden on society, one that is comparable to the financial burden of heart disease and cancer. Due to its insidious onset, cognitive impairment can be clinically silent for several years; therefore, diagnosis occurs late in the disease process, and treatment becomes almost useless. The identification of predictors of dementia may help identify the pathophysiological mechanisms underlying the disease and lead to the development of a more effective medical diagnosis and therapy, and thus an early treatment. Review of the literature suggests that in those individuals with less cognitive impairment (normal/predementia group), hearing loss has an association with language comprehension, and when cognitive impairment increases (moderate or severe dementia group), the contributing effect of hearing loss as a cognitive ability-impairing factor also increases. Greater understanding of the links between hearing impairment and cognition may have important implications for the screening and diagnosis of cognitive decline in older people with hearing impairment.
Speech Perception and Information-Carrying Capacity for Hearing Aid Users of Different Ages
Authors: Hoppe Ulrich , Hocke Thomas , Müller Alexander , Hast Anne
Published: November 2016

Hearing impairment in the elderly is usually treated with conventional hearing aids; however, a large number of older people do not achieve sufficient speech recognition with hearing aids. The aim of the study was to describe speech perception with hearing aids in comparison to pure-tone hearing loss and maximum speech recognition scores for phonemically balanced words. Data from 392 hearing aid users with different degrees of hearing loss were evaluated retrospectively. In particular, pure-tone thresholds, the maximum monosyllabic word score, and the monosyllabic word score in quiet at conversational level with a hearing aid were analysed. The results showed that speech perception scores decline with increasing age. Even when corrected for pure-tone hearing loss, a significant decline in speech recognition scores after the age of 80 years was observed. Regarding the maximum monosyllabic word score, the effect is smaller but still observable; thus, speech recognition with hearing aids is significantly lower for older subjects. This can be attributed partially to the reduction of the information-carrying capacity in this group.
Lymphadenectomy Specimens in a Large Retrospective Cohort of Pediatric Patients Reveal No in situ Lymphomas but a Broad Spectrum of Reactive Changes
Authors: Banz Yara , Tzankov Alexandar , Dirnhofer Stephan , Perren Aurel , Hoeller Sylvia
Published: November 2016

Objectives: While the incidence and prevalence of in situ follicular neoplasia (ISFN) and in situ mantle cell neoplasia (ISMCN) in adults are well documented, little is known about these early (precursor) lesions in pediatric populations. The aim of this study was to analyze so-called ‘reactive' lymph nodes harvested for the purpose of staging solid tumors, unexplained lymphadenopathies, or presumed inflammatory processes or in conjunction with other surgical interventions in children and adolescents aged <18 years, with special attention to ISFN and ISMCN. Methods: Formalin-fixed, paraffin-embedded reactive lymph node samples from an unselected pediatric population from two catchment areas in Switzerland were retrospectively analyzed for the presence of ISFN and ISMCN and specific reactive lymph node patterns. Results: While a diverse range of histopathological patterns of reactive lymph node changes with a particular periodic increase in mycobacterioses could be observed in this pediatric population, not a single case of ISFN or ISMCN was found. Conclusions: Early histological lymphomagenesis equivalents in the form of in situ lymphomas are exceedingly rare events in children and young adolescents. The spectrum of reactive lymph node changes is large, with differences possibly determined by regional variations in geography, demographics, catchment areas, seasons, and years, respectively.
Feasibility and Efficacy of a Urologic Profession Campaign on Cryptorchidism Using Internet and Social Media
Authors: Borgmann Hendrik , Kliesch Sabine , Roth Stephan , Roth Mael , Degener Stephan
Published: November 2016

Introduction: We performed a professional campaign in Germany intending to establish the urologic profession as a competent and helpful point of contact for patients with cryptorchidism. The aim of this study was to assess the feasibility of this campaign and to quantify the efficacy of using Internet vs. social media. Materials and Methods: The strategic design of the campaign comprised a strategy meeting, creation of a landing page, and targeted advertisements on Google in the form of Adwords and on Facebook in the form of sidebar ads and sponsored posts. Outcome measurements were number of impressions, homepage sessions, and downloads of an information brochure. Results: The campaign generated 2,511,923 impressions, 7,369 homepage sessions and 1,086 downloads of information brochures using a total investment budget of 7,500€. Use of Google Adwords was more efficient on outcome measurements than Facebook. A subanalysis of Facebook advertisements showed that sidebar ads and sponsored posts were equally efficient. Conclusions: New media are an effective platform for a profession campaign. Google Adwords is a more effective and cost-efficient platform than Facebook for a targeted campaign.
Historical Perspective of Split Cord Malformations: A Tale of Two Cords
Authors: Saker Erfanul , Loukas Marios , Fisahn Christian , Oskouian Rod J. , Tubbs R. Shane
Published: November 2016

Introduction: Our appreciation and understanding of what is now known as the split cord malformation (SCM) have a long history. The oldest known example of SCM is from roughly AD 100. Other isolated examples can be found in the large body of work of the pathologists of the 1800s, where the SCMs were found incidentally during autopsies. Conclusions: SCM has a rich history and has intrigued physicians for over 200 years. Many well-known figures from the past such as Chiari and von Recklinghausen, both pathologists, made early postmortem descriptions of SCM. With the advent of MRI, these pathological embryological derailments can now often be detected and appreciated early and during life. Our understanding and ability to treat these congenital malformations as well as the terminology used to describe them have changed over the last several decades.
IAC Standardized Reporting of Breast Fine-Needle Aspiration Biopsy Cytology
Authors: Field Andrew S. , Schmitt Fernando , Vielh Philippe
Published: November 2016

There have been many changes in the roles of fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) in the diagnostic workup of breast lesions in routine breast clinics and in mammographic breast screening programs, as well as changes in the management algorithms utilized and the treatments available, since the NCI consensus on breast FNAB cytology in 1996. A standardized approach will improve training and performance of FNAB and smear-making techniques, and structured reporting will improve the quality and reproducibility of reports across departments, cities and countries providing a basis for quality assurance measures and improving patient care and facilitating research. Linking cytology reports to management algorithms will increase the clinicians' use of FNAB cytology and where appropriate CNB, and enhance the use of ancillary tests for prognostic testing. The IAC recognizes that the local medical infrastructure and resources for breast imaging, biopsy and treatment will influence the diagnostic workup and management of breast disease, but best practice guidelines should be established and modified as required.
The Genetic Predisposition Score of Seven Obesity-Related Single Nucleotide Polymorphisms Is Associated with Better Metabolic Outcomes after Roux-en-Y Gastric Bypass
Authors: Nicoletti Carolina Ferreira , Pinhel Marcela A. Souza , de Oliveira Bruno Affonso Parenti , Marchini Julio Sergio , Salgado Junior Wilson , Silva Junior Wilson Araujo , Nonino Carla Barbosa
Published: November 2016

Background/Aims: Genetic variants associated with obesity have cumulative effects on obesity risk and related phenotypes. This study aimed to estimate the contribution of a genetic predisposition score (GPS) calculated from 7 obesity-related polymorphisms to the improvement of biochemical parameters 1 year after Roux-en-Y gastric bypass (RYGB). Methods: Obese patients (n = 150; aged 47.2 ± 10.5 years) were enrolled and weight, body mass index (BMI), and biochemical parameters (glycemia and lipid profile) were evaluated preoperatively and 1 year after RYGB. A GPS was calculated with the polymorphisms rs1801282 of PPARG2, rs4994 of ADRB3, rs1800592 of UCP1, rs659366 and rs669339 of UCP2, rs7121 of GNAS1, and rs5443 of GNB3. We observed that 66.3% of the patients has a GPS >5. Results: During the preoperative period, the GPS showed a significant association with weight (β = -0.163; p = 0.020), BMI (β = -0.169; p = 0.038), and glucose concentrations (β = -0.177; p = 0.036). After sex and age adjustment, a higher GPS was associated with a greater reduction in glycemia (β = -0.158; p = 0.048), triglycerides (β = -0.256; p = 0.002), and total cholesterol (β = -0.172; p = 0.038) concentrations 1 year after surgery. Conclusion: Our data elucidated that a higher GPS provides a greater metabolic benefit of RYGB.
Etiologic and Clinical Characterization of Patients with Recurrent Spontaneous Intracerebral Hemorrhage
Authors: Wolf Marc E. , Alonso Angelika , Ebert Anne D. , Szabo Kristina , Chatzikonstantinou Anastasios
Published: November 2016

Background: The impact of recurrent stroke has been extensively addressed with regard to ischemic stroke, revealing potentially different etiologies of recurrent events in the individual patient. In contrast, data on recurrent intracerebral hemorrhage (ICH) are scarce, especially considering etiologic characterization. We aimed to determine the etiology of recurrent ICH at each event to identify potential etiologic changes. Patients and Methods: We analyzed the data of patients admitted to our stroke unit with recurrent ICH between 1998 and 2014 with regard to clinical characteristics and etiology. Results: Thirty-three patients (2.6%) with recurrent ICH were identified. Mean age (mean ± SD) at the initial event was 69 ± 9 and 72 ± 9 years at recurrence. Median interval between events was 18 months. Mean National Institutes of Health Stroke Scale (first/second event) was 4/9 at admission and 2/8 at discharge. Over 30% of patients developed symptomatic epilepsy. Etiologic distribution was (first/second event) the following: probable cerebral amyloid angiopathy (CAA) (12/20), possible CAA (3/0), hypertensive (5/4), anticoagulation (4/3), vascular malformation (2/4), ischemia with secondary hemorrhage (4/0), vasculitis (0/1), undetermined (4/0). Conclusions: Recurrent ICH is rare, CAA being its most common etiology. Etiology of ICH may differ between the first/second event in about 10%. The findings indicate the need of a complete and distinct work-up including MRI in every instance of ICH recurrence.
Functional Assessment of Coronary Artery Disease in Patients Undergoing Transcatheter Aortic Valve Implantation
Authors: Pesarini Gabriele , Scarsini Roberto , Zivelonghi Carlo , Piccoli Anna , Gambaro Alessia , Gottin Leonardo , Rossi Andrea , Ferrero Valeria , Vassanelli Corrado , Ribichini Flavio
Published: November 2016

Background—

Aortic valve stenosis may influence fractional flow reserve (FFR) of concomitant coronary artery disease by causing hypertrophy and reducing the vasodilatory reserve of the coronary circulation. We sought to investigate whether FFR values might change after valve replacement.

Methods and Results—

The functional relevance of 133 coronary lesions was assessed by FFR in 54 patients with severe aortic valve stenosis before and after transcatheter aortic valve implantation (TAVI) during the same procedure. A linear mixed model was used to verify the interaction of TAVI effect with the FFR values. No significant overall change in FFR values was found before and after the aortic valve stenosis removal (0.89±0.10 versus 0.89±0.13;
P
=0.73). A different trend in FFR groups (positive if ≤0.8; negative if >0.8) was found after TAVI (
P
for interaction <0.001). Positive FFR values worsened after TAVI (0.71±0.11 versus 0.66±0.14). Conversely, negative FFR values improved after TAVI (0.92±0.06 versus 0.93±0.07). Similarly, FFR values in coronary arteries with lesions presenting percent diameter stenosis >50 worsened after TAVI (0.84±0.12 versus 0.82±0.16;
P
=0.02), whereas FFR values in arteries with mild lesions (percent diameter stenosis <50) tended toward improvement after TAVI (0.90±0.07 versus 0.91±0.09;
P
=0.69). Functional FFR variations after TAVI changed the indication to treat the coronary stenosis in 8 of 133 (6%) lesions.

Conclusions—

Coronary hemodynamics are influenced by aortic valve stenosis removal. Nevertheless, FFR variations after TAVI are minor and crossed the diagnostic cutoff of 0.8 in a small number of patients after valve replacement. Borderline coronary lesions might become functionally significant after valve replacement, although FFR-guided interventions were infrequent even in patients with angiographically significant lesions.
Insulin-Like Growth Factor 1 Receptor-Dependent Pathway Drives Epicardial Adipose Tissue Formation After Myocardial Injury
Authors: Zangi Lior , Oliveira Marcela S. , Ye Lillian Y. , Ma Qing , Sultana Nishat , Hadas Yoav , Chepurko Elena , Später Daniela , Zhou Bin , Chew Wei Leong , Ebina Wataru , Abrial Maryline , Wang Qing-Dong , Pu William T. , Chien Kenneth R.
Published: November 2016

Background:

Epicardial adipose tissue volume and coronary artery disease are strongly associated, even after accounting for overall body mass. Despite its pathophysiological significance, the origin and paracrine signaling pathways that regulate epicardial adipose tissue’s formation and expansion are unclear.

Methods:

We used a novel modified mRNA-based screening approach to probe the effect of individual paracrine factors on epicardial progenitors in the adult heart.

Results:

Using 2 independent lineage-tracing strategies in murine models, we show that cells originating from the Wt1
+
mesothelial lineage, which includes epicardial cells, differentiate into epicardial adipose tissue after myocardial infarction. This differentiation process required Wt1 expression in this lineage and was stimulated by insulin-like growth factor 1 receptor (IGF1R) activation. IGF1R inhibition within this lineage significantly reduced its adipogenic differentiation in the context of exogenous, IGF1-modified mRNA stimulation. Moreover, IGF1R inhibition significantly reduced Wt1 lineage cell differentiation into adipocytes after myocardial infarction.

Conclusions:

Our results establish IGF1R signaling as a key pathway that governs epicardial adipose tissue formation in the context of myocardial injury by redirecting the fate of Wt1
+
lineage cells. Our study also demonstrates the power of modified mRNA -based paracrine factor library screening to dissect signaling pathways that govern progenitor cell activity in homeostasis and disease.
Shepherd’s Enemy or Aşina, Böri, Börte Činō, and Bozkurt?
Authors: Worringer Renée
Published: November 2016

Wolves have been a constant in human consciousness, whether they are considered supernatural beings, nurturers and guides for humankind, or powerful or malevolent predators. Attitudes toward wolves in Western Christian societies have been overwhelmingly negative due to perceptions of wolves as preying upon souls and flocks. Pre-modern Turco-Mongolian views of wolves were generally positive, as she-wolves, ancestral deities, or guides for nomadic warriors, even after conversion to Islam. This Turco-Mongolian perspective allows the wolves some protection against human aggression in Turkic and Mongolian regions in the present.
Stretching the Joint Criminal Enterprise Doctrine to the Extreme: When Culpability and Liability Do Not Match
Authors: Perova Natalia
Published: November 2016

Joint criminal enterprise (jce) has caused a lot of concern amongst international criminal law practitioners and academics since its first appearance at the ad hoc Tribunals. A recent landmark decision, by the uk Supreme Court in Jogee, that overruled 30 years of common law development on joint enterprise, stimulates further discussions on whether jce in its current form fairly reflects the balance between culpability and corresponding liability of the defendant. This article explores this issue by suggesting that the level of culpability of defendants does not match the degree of liability they incur under jce iii. The article dissects the jce iii mode of liability by considering it a ‘two-crime liability’: a common purpose crime and a foreseeable crime, and compares it with aiding/abetting. This article argues that the level of culpability of defendants under jce iii is much lower than their liability for the crimes they are convicted of.
The International Criminal Court and the Complex Road to Peace in Côte d’ Ivoire
Authors: Malu Linus Nnabuike
Published: November 2016

After over ten years of violent conflicts and atrocities, Côte d’ Ivoire is gradually returning to peace and economic prosperity, but the road to peace is complex. This article examines the violent conflicts in the country, and how the involvement of the International Criminal Court (icc) impacts on the peace process in the country. It examines whether the icc is complicating or facilitating the peace process by relying on four variables: deterrence, accountability to the law, reconciliation and victims’ rights. This article argues that the impacts of the icc on the peace process is multi-dimensional, and concludes that the icc impacts on the peace process in the country in minimal but subtle ways by influencing deterrence and accountability to the law.
Two new species of Viola (Violaceae) named in honor of preceding Peruvian botanists
Authors: GONZÁLES PAÚL , CANO ASUNCIÓN
Published: November 2016

We describe and illustrate Viola ferreyrae and Viola enmae (Violaceae), two new species of Viola section Andinium, both from the high Andes of southeastern Peru. Viola ferreyrae is named in honor of Ramón Ferreyra and Viola enmae in honor of Enma Cerrate, two Peruvian botanists who have greatly contributed to Peruvian botany. Viola ferreyrae is similar to Viola granulosa by its white flowers with purple lines and lack of a spur, but differs in having pinnatifid to pinnatipartite leaves, two pairs of stipules located at two different positions, and the upper surface of the leaf blade reticulate-alveolate (not granulose). Viola enmae is similar to Viola calchaquiensis by its small, crenulate and spathulate leaves, undulate crenulations, lacking stipules, upper and lateral petals oblong-obovate and reflexed, style apex truncated with margin trilobed, but differs in having blade narrowed, margins bearing 2(–3) undulate crenulations per side, bracteoles short, petals smaller, lateral petals smooth (not papillose-bearded), and lowermost petals somewhat emarginate.
Robust Identification of Local Biogeophysical Effects of Land-Cover Change in a Global Climate Model
Authors: Winckler J. , Reick C. H. , Pongratz J.
Published: November 2016

Land-cover change (LCC) happens locally. However, in almost all simulation studies assessing biogeophysical climate effects of LCC, local effects (due to alterations in a model grid box) are mingled with nonlocal effects (due to changes in wide-ranging climate circulation). This study presents a method to robustly identify local effects by changing land surface properties in selected “LCC boxes” (where local plus nonlocal effects are present), while leaving others unchanged (where only nonlocal effects are present). While this study focuses on the climate effects of LCC, the method presented here is applicable to any land surface process that is acting locally but is capable of influencing wide-ranging climate when applied on a larger scale. Concerning LCC, the method is more widely applicable than methods used in earlier studies. The study illustrates the possibility of validating simulated local effects by comparison to observations on a global scale and contrasts the underlying mechanisms of local and nonlocal effects. In the MPI-ESM, the change in background climate induced by extensive deforestation is not strong enough to influence the local effects substantially, at least as long as sea surface temperatures are not affected. Accordingly, the local effects within a grid box are largely independent of the number of LCC boxes in the isolation approach.