bluuebunny/crossref_metadata_2025 huggingface dataset:
Pro‐gastrin‐releasing peptide and outcome in patients with heart failure and anaemia: results from the RED‐HF study
Authors: Ueland Thor , Gullestad Lars , Kou Lei , Aukrust Pål , Anand Inderjit S. , Broughton Marianne Nordlund , McMurray John J. , van Veldhuisen Dirk J. , Warren David J. , Bolstad Nils
Published: August 2018

Aims

Neuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin‐releasing peptide (GRP), derived from the precursor proGRP1‐125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction.

Methods and results

The association between plasma proGRP (time‐resolved immunofluorometric assay) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anaemia, enrolled in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED‐HF) trial. Median proGRP levels in the RED‐HF cohort were markedly increased [95 ng/L (25th, 75th percentile, 69–129 ng/L)] with 64% patients above the 80 ng/L reference limit. Baseline proGRP correlated with estimated glomerular filtration rate (r = 0.52), N terminal pro brain natriuretic peptide (r = 0.33), troponin T (r = 0.34), and haemoglobin (r = 0.16) (all P < 0.001). The incidence outcome increased with increasing tertiles of baseline proGRP (primary endpoint third tertile vs. the lowest tertile; hazard ratio 1.91; 95% confidence interval 1.60–2.28, P < 0.001). However, these associations were markedly attenuated and non‐significant in adjusted models. No interaction between baseline proGRP and the effect of darbepoetin alfa treatment was detected. Moreover, no significant association between changes in proGRP during 6 month follow‐up and outcome was observed.

Conclusions

Pro‐gastrin‐releasing peptide is increased in patients with HF with reduced ejection fraction and anaemia, in particular in patients with poor renal function. However, proGRP adds little as a prognostic marker on top of conventional HF risk factors.
Abnormal neural response to phonological working memory demands in persistent developmental stuttering
Authors: Yang Yang , Jia Fanlu , Fox Peter T. , Siok Wai Ting , Tan Li Hai
Published: August 2018

Persistent developmental stuttering is a neurological disorder that commonly manifests as a motor problem. Cognitive theories, however, hold that poorly developed cognitive skills are the origins of stuttering. Working memory (WM), a multicomponent cognitive system that mediates information maintenance and manipulation, is known to play an important role in speech production, leading us to postulate that the neurophysiological mechanisms underlying stuttering may be associated with a WM deficit. Using functional magnetic resonance imaging, we aimed to elucidate brain mechanisms in a phonological WM task in adults who stutter and controls. A right‐lateralized compensatory mechanism for a deficit in the rehearsal process and neural disconnections associated with the central executive dysfunction were found. Furthermore, the neural abnormalities underlying the phonological WM were independent of memory load. This study demonstrates for the first time the atypical neural responses to phonological WM in PWS, shedding new light on the underlying cause of stuttering.
Pharmacoproteomics Profiling of Plasma From β‐Thalassemia Patients in Response to Hydroxyurea Treatment
Authors: Zohaib Muhammad , Ansari Saqib H. , Shamsi Tahir S. , Zubarev Roman A. , Zarina Shamshad
Published: August 2018

β‐Thalassemia is a genetic disorder caused by defects in the β‐globin gene resulting in the absence or reduced synthesis of adult hemoglobin (HbA). Hydroxyurea is an effective drug to increase fetal γ‐globin (HbF) expression, replacing the missing adult β‐globin. The mechanism of HbF induction by hydroxyurea and improvement in clinical symptoms are still poorly understood. In the present study we performed comparative analysis of plasma proteome in pre– and post–hydroxyurea‐treated β‐thalassemia major transfusion‐dependent children (n = 10, mean age = 3.2 years) as well as responders versus nonresponders to hydroxyurea treatment. Plasma was collected before and after 6 months of hydroxyurea treatment, with patients subcategorized on the basis of their response to hydroxyurea. Among 400 identified proteins using a label‐free quantitative proteomics approach, 28 proteins were found to be significantly different in pre– versus post–hydroxyurea‐treated groups, with transferrin receptor protein‐1 being most downregulated and hemopexin and haptoglobin the most upregulated proteins after treatment. In responder versus nonresponder comparison, 26 proteins were found to be differentially expressed, with carbonic anhydrase 1, hemoglobin subunit γ‐1, and peroxiredoxin‐2 showing the significant changes. The mechanism of hydroxyurea treatment in β‐thalassemia patients appears to be complex, requiring a large sample size and a longer period of treatment to reveal its details.
Value of MRI in medicine: More than just another test?
Authors: van Beek Edwin J.R. , Kuhl Christiane , Anzai Yoshimi , Desmond Patricia , Ehman Richard L. , Gong Qiyong , Gold Garry , Gulani Vikas , Hall‐Craggs Margaret , Leiner Tim , Lim C.C. Tschoyoson , Pipe James G. , Reeder Scott , Reinhold Caroline , Smits Marion , Sodickson Daniel K. , Tempany Clare , Vargas H. Alberto , Wang Meiyun
Published: August 2018

There is increasing scrutiny from healthcare organizations towards the utility and associated costs of imaging. MRI has traditionally been used as a high‐end modality, and although shown extremely important for many types of clinical scenarios, it has been suggested as too expensive by some. This editorial will try and explain how value should be addressed and gives some insights and practical examples of how value of MRI can be increased. It requires a global effort to increase accessibility, value for money, and impact on patient management. We hope this editorial sheds some light and gives some indications of where the field may wish to address some of its research to proactively demonstrate the value of MRI.

Level of Evidence: 5

Technical Efficacy: Stage 5

J. Magn. Reson. Imaging 2019;49:e14–e25.
Modelling the impacts of projected sea ice decline on the low atmosphere and near‐surface permafrost on the North Slope of Alaska
Authors: Cai Lei , Alexeev Vladimir A. , Arp Christopher D. , Jones Benjamin M. , Romanovsky Vladimir E.
Published: August 2018

This model‐based study assesses the response of the lower atmosphere and near‐surface permafrost on the North Slope of Alaska to projections in sea ice decline. The Weather Research and Forecast model, with polar optimization (polar WRF), was configured for the North Slope of Alaska and the adjacent Arctic Ocean and run for two decade‐long control periods, the 1970s and the 2040s. Community Earth System Model output was used to drive the polar WRF model. By swapping the sea ice coverage in the control cases, two polar WRF sensitivity experiments were designed to quantify the changes in the low atmosphere and near‐surface permafrost in response to projected declines in sea ice extent. The strongest impacts of sea ice decline occur primarily during the late fall and early winter. These include increases in surface air temperature, surface humidity, total cloud cover, and precipitation amount. Future impacts of sea ice decline are projected to become weaker over time in the late fall and early winter while becoming more prominent in late spring and early summer. Projected sea ice decline also inhibits low‐level cloud formation in summer as a result of destabilization of the boundary layer. Sensitivity experiments by polar WRF and Geophysical Institute Permafrost Laboratory model, respectively, suggest that sea ice decline explains approximately 20% of both the atmospheric and permafrost warmings on a mean annual basis compared to the overall projected warming under the RCP4.5 scenario.
Olfactory implant: Demand for a future treatment option in patients with olfactory dysfunction
Authors: Besser Gerold , Liu David T. , Renner Bertold , Hummel Thomas , Mueller Christian A.
Published: August 2018

Objectives

Therapeutic options in olfactory dysfunction (OD) are limited. Numerous studies have shown impact of OD on quality of life. Lately, various studies support benefits of olfactory training, but therapy‐refractory cases leave doctors and patients locked in a stalemate. An olfactory implant (OI), in analogy to the widely successful cochlear implant, still seems far away from realization. The present study sought to evaluate the demand of OI in patients with OD.

Methods

Sixty‐one patients (28 females and 33 males, mean age/standard deviation 54.9/17.6 years) with OD were recruited. We performed olfactory testing for threshold (T), discrimination (D), and identification (I) using Sniffin' Sticks; summed scores (TDI) allowed us to determine normosmia, hyposmia, and anosmia. We applied questionnaires on the importance of smell (IOS), on olfactory disorders (QOD) and on the interest/willingness for OI, considering the need for skull base/head surgery.

Results

Twenty‐one patients (34.4%) stated that OI could be a future treatment option for them. This decision significantly correlated with TDI, I, complaint‐related questions of the QOD, and IOS (P < .05).

Conclusion

With approximately one‐third of patients considering OI as a therapy option, this study seems to indicate a demand for OI. In selected patients, with a high degree of complaints, low olfactory test scores, and maybe an additional occupational need for olfactory function, OI might be an option if future developments warrant safety of OI procedures.

Level of Evidence

4 Laryngoscope, 129:312–316, 2019
“My Dog Deafened Me!”: Case Report of Capnocytophaga canimorsus Infection and Literature Review
Authors: Cadre Barbara , Al Oraimi Mouna , Grinholtz‐Haddad Julia , Benkhatar Hakim
Published: August 2018

Capnocytophaga canimorsus infection is an emerging zoonotic disease that could cause meningitis and subsequent sensorineural hearing loss (SNHL), especially in the immunocompromised population. It is a gram‐negative rod that belongs to the normal oral flora of dogs and cats and may be transmitted to humans by biting or licking. Our case report and literature review showed that this postmeningitic SNHL has distinct features from common bacterial meningitis‐related SNHL. We therefore discuss the diagnostic, therapeutic, and preventive aspects of this uncommon cause of SNHL. Because it is now the second‐most common dog‐bite transmitted pathogen, otolaryngologists are more likely to encounter this zoonotic disease and should be aware of its characteristics. Laryngoscope, 129:41–43, 2019
The iron limitation mosaic in the California Current System: Factors governing Fe availability in the shelf/near‐shelf region
Authors: Till C. P. , Solomon J. R. , Cohen N. R. , Lampe R. H. , Marchetti A. , Coale T. H. , Bruland K. W.
Published: August 2018

The California Current System is a productive eastern boundary region off the coasts of Washington, Oregon, and California. There is strong seasonality to the region, with high levels of rainfall and river input to the coastal ocean during the winter season, and coastal and Ekman upwelling during the spring and summer. Iron (Fe) input to the coastal ocean during the winter months can be stored in the continental shelf mud belts and then be delivered to the surface ocean by upwelling in the spring and summer. There have been a number of studies providing strong evidence of Fe‐limitation of diatom growth occurring in regions of the California Current System off of California, and the occurrence of Fe‐limitation has been linked with narrow continental shelf mud belt width and low river input. We provide evidence for potential Fe‐limitation of diatoms off the southern coast of Oregon in July 2014, just off the shelf break near Cape Blanco in a region with moderate shelf width and river input. Since eastern boundary regions account for a disproportionally large amount of global primary production, this observation of potential Fe‐limitation in an unexpected near‐shore region of the California Current System has implications for global models of primary productivity. In order to re‐evaluate the factors impacting Fe availability, we utilize satellite imagery to compare with historical datasets, and show that unexpected levels of Fe can often be explained by eddies, plumes of upwelled water moving offshore, or lack of recent upwelling.
Splenectomy as Flow Modulation Strategy and Risk Factors of De Novo Portal Vein Thrombosis in Adult‐to‐Adult Living Donor Liver Transplantation
Authors: Linares Ivan , Goldaracena Nicolas , Rosales Roizar , Maza Luis De la , Kaths Moritz , Kollmann Dagmar , Echeverri Juan , Selzner Nazia , McCluskey Stuart A. , Sapisochin Gonzalo , Lilly Leslie B. , Greig Paul , Bhat Mamatha , Ghanekar Anand , Cattral Mark , McGilvray Ian , Grant David , Selzner Markus
Published: August 2018

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult‐to‐adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no‐PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t‐PVT]; n = 28). Ten patients had early portal vein thrombosis (e‐PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l‐PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t‐PVT (hazard ratio [HR], 3.55; P = 0.01), e‐PVT (HR, 4.96; P = 0.04), and l‐PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l‐PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e‐PVT and l‐PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no‐PVT, 2% versus e‐PVT, 10%; P = 0.15). No significant differences were found regarding 1‐year (89% versus 92%), 5‐year (79% versus 82%), and 10‐year (69% versus 79%) graft survival between the t‐PVT and no‐PVT groups, respectively (P = 0.24). The 1‐year (89% versus 96%), 5‐year (82% versus 86%), and 10‐year (79% versus 83%) patient survival was similar for the patients in the no‐PVT and t‐PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.
Validation of the MDS clinical diagnostic criteria for Parkinson's disease
Authors: Postuma Ronald B. , Poewe Werner , Litvan Irene , Lewis Simon , Lang Anthony E. , Halliday Glenda , Goetz Christopher G. , Chan Piu , Slow Elizabeth , Seppi Klaus , Schaffer Eva , Rios‐Romenets Silvia , Mi Taomian , Maetzler Corina , Li Yuan , Heim Beatrice , Bledsoe Ian O. , Berg Daniela
Published: August 2018

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease. These criteria aimed to codify/reproduce the expert clinical diagnostic process and to help standardize diagnosis in research and clinical settings. Their accuracy compared with expert clinical diagnosis has not been tested. The objectives of this study were to validate the International Parkinson and Movement Disorder Society diagnostic criteria against a gold standard of expert clinical diagnosis, and to compare concordance/accuracy of the International Parkinson and Movement Disorder Society criteria to 1988 United Kingdom Brain Bank criteria.

Methods: From 8 centers, we recruited 626 parkinsonism patients (434 PD, 192 non‐PD). An expert neurologist diagnosed each patient as having PD or non‐PD, regardless of International Parkinson and Movement Disorder Society criteria (gold standard, clinical diagnosis). Then a second neurologist evaluated the presence/absence of each individual item from the International Parkinson and Movement Disorder Society criteria. The overall accuracy/concordance rate, sensitivity, and specificity of the International Parkinson and Movement Disorder Society criteria compared with the expert gold standard were calculated.

Results: Of 434 patients diagnosed with PD, 94.5% met the International Parkinson and Movement Disorder Society criteria for probable PD (5.5% false‐negative rate). Of 192 non‐PD patients, 88.5% were identified as non‐PD by the criteria (11.5% false‐positive rate). The overall accuracy for probable PD was 92.6%. In addition, 59.3% of PD patients and only 1.6% of non‐PD patients met the International Parkinson and Movement Disorder Society criteria for clinically established PD. In comparison, United Kingdom Brain Bank criteria had lower sensitivity (89.2%, P = 0.008), specificity (79.2%, P = 0.018), and overall accuracy (86.4%, P < 0.001). Diagnostic accuracy did not differ according to age or sex. Specificity improved as disease duration increased.

Conclusions: The International Parkinson and Movement Disorder Society criteria demonstrated high sensitivity and specificity compared with the gold standard, expert diagnosis, with sensitivity and specificity both higher than United Kingdom Brain Bank criteria. © 2018 International Parkinson and Movement Disorder Society
Harnessing the power of placebos in movement disorders: Insights from Parkinson's disease in clinical research and practice
Authors: Mestre Tiago A. , Shamy Michel , Benedetti Fabrizio , Lang Anthony E.
Published: August 2018

The placebo effect alongside the detrimental nocebo and lessebo effects associated with the use of placebos are well‐recognized phenomena. Research conducted in the last two decades has demonstrated that the placebo effect is a measurable health benefit with well‐known neurobiological correlates. In this review, we describe the current knowledge about how to best make use of the placebo effect to improve clinical research and optimize clinical care. We will cover four key topics: (1) setting the stage: historical perspectives on the use of placebos; (2) optimizing the use of placebos in clinical trials; (3) use of placebos in clinical practice; and (4) how can we minimize the ethical risks of using placebos? The adoption of the placebo‐controlled trial as a standard in the therapeutic development reduced the placebo effect to background noise in a therapeutic signal. Strategies to minimize the placebo effect in clinical trials have been used to obtain positive efficacy results. In more recent years, new study paradigms encouraged a change in the views on placebos and the placebo effect. Alternative study designs and the development of biomarkers for a placebo response permit a better understanding of the contribution of the placebo effect to the results of interventional studies, without minimizing it. In clinical practice, optimizing the placebo effect (and reducing nocebo effects) has the potential to improve care for our patients, but raises ethical challenges. An enhanced patient‐physician relationship would be central to any evidence‐based intervention used in clinical care to heighten the placebo effect. © 2018 International Parkinson and Movement Disorder Society
Progressive myoclonus ataxia: Time for a new definition?
Authors: van der Veen Sterre , Zutt Rodi , Elting Jan Willem J. , Becker Charlotte E. , de Koning Tom J. , Tijssen Marina A.J.
Published: August 2018

Background: The clinical demarcation of the syndrome progressive myoclonus ataxia is unclear, leading to a lack of recognition and difficult differentiation from other neurological syndromes.

Objectives: The objective of this study was to apply a refined definition of progressive myoclonus ataxia and describe the clinical characteristics in patients with progressive myoclonus ataxia and with isolated cortical myoclonus.

Methods: A retro‐ and prospective analysis was performed in our tertiary referral center between 1994 and 2014. Inclusion criteria for progressive myoclonus ataxia patients were the presence of myoclonus and ataxia with or without infrequent (all types, treatment responsive) epileptic seizures. Inclusion criteria for isolated cortical myoclonus was the presence of isolated cortical myoclonus. Clinical and electrophysiological characteristics data were systematically scored.

Results: A total of 14 progressive myoclonus ataxia patients (males, 7; females, 7), median age 14.5 years, and 8 isolated cortical myoclonus patients (males, 2; females, 6), median age 23.5 years, were identified. In 93% of the progressive myoclonus ataxia patients, ataxia started first (median 2 years) followed by myoclonus (4 years) and finally infrequent epilepsy (9.3 years), with a progressive course in 93%. In 64% of the progressive myoclonus ataxia patients, a genetic underlying etiology was identified, including 3 not earlier reported causative progressive myoclonus ataxia genes. In isolated cortical myoclonus patients, myoclonus started at (median) 12 years with progression over time in 63% and a single epileptic seizure in 1 patient. No genetic causes were identified.

Conclusion: Using a refined definition, we could create a rather homogenous progressive myoclonus ataxia group. Patients with isolated cortical myoclonus have a different course and do not appear to evolve in progressive myoclonus ataxia. The refined progressive myoclonus ataxia definition is a successful first step toward creating a separate syndrome for both clinical practice and future genetic research. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Higher serum cholesterol and decreased Parkinson's disease risk: A statin‐free cohort study
Authors: Rozani Violetta , Gurevich Tanya , Giladi Nir , El‐Ad Baruch , Tsamir Judith , Hemo Beatriz , Peretz Chava
Published: August 2018

Background: Higher levels of serum cholesterol are well‐established risk factors for coronary artery disease and stroke. The role of serum cholesterol in neurodegeneration is not clear.

Objective: We evaluated the association between serum cholesterol levels over time and the risk of Parkinson's disease (PD) among statin‐free individuals.

Methods: A population‐based cohort study of 261,638 statin‐free individuals (aged 40‐79 years at their first serum cholesterol test, 42.7% men), with repeated measures of total, low, and high‐density lipoprotein cholesterol was performed from 1999 to 2012. Individuals were followed from their first cholesterol test until PD incidence, death, or end of study. The PD incidence was assessed using a validated antiparkinsonian‐drug tracing approach. Cox models stratified by sex and age with time‐dependent cholesterol variables were applied to estimate PD hazard ratios.

Results: A total of 764 (3.3% patients aged 65 + years) incident PD cases were detected during a mean follow‐up of 7.9 (±3.6) years. Among men, the middle and upper tertiles of total and low‐density lipoprotein cholesterol compared to the lowest were significantly associated with a lower PD risk. Age‐pooled hazard ratios (95% confidence interval) for middle and upper tertiles were 0.82 (0.66‐1.01) and 0.71 (0.55‐0.93), respectively, for total cholesterol, and 0.80 (0.65‐0.98) and 0.72 (0.54‐0.95) respectively, for low‐density lipoprotein cholesterol. Among women, the association between total and low‐density lipoprotein cholesterol levels with PD risk was not significant. Null results were found for both sexes for high‐density lipoprotein cholesterol.

Conclusions: Higher levels of total and low‐density lipoprotein cholesterol among men over time indicated a decreased PD risk. The potential role of cholesterol in disease protection warrants further investigation. © 2018 International Parkinson and Movement Disorder Society
Longer β oscillatory episodes reliably identify pathological subthalamic activity in Parkinsonism
Authors: Deffains Marc , Iskhakova Liliya , Katabi Shiran , Israel Zvi , Bergman Hagai
Published: August 2018

Background: The efficacy of deep brain stimulation (DBS) ‐ primarily of the subthalamic nucleus (STN) ‐ for advanced Parkinson's disease (PD) is commonly attributed to the suppression of pathological synchronous β oscillations along the cortico‐thalamo‐basal ganglia network. Conventional continuous high‐frequency DBS indiscriminately influences pathological and normal neural activity. The DBS protocol would therefore be more effective if stimulation was only applied when necessary (closed‐loop adaptive DBS).

Objectives and Methods: Our study aimed to identify a reliable biomarker of the pathological neuronal activity in parkinsonism that could be used as a trigger for adaptive DBS. To this end, we examined the oscillatory features of paired spiking activities recorded in three distinct nodes of the basal ganglia network of 2 African green monkeys before and after induction of parkinsonism (by MPTP intoxication).

Results: Parkinsonism‐related basal ganglia β oscillations consisted of synchronized time‐limited episodes, rather than a continuous stretch, of β oscillatory activity. Episodic basal ganglia β oscillatory activity, although prolonged in parkinsonism, was not necessarily pathological given that short β episodes could also be detected in the healthy state. Importantly, prolongation of the basal ganglia β episodes was more pronounced than their intensification in the parkinsonian state—especially in the STN. Hence, deletion of longer β episodes was more effective than deletion of stronger β episodes in reducing parkinsonian STN synchronized oscillatory activity.

Conclusions: Prolonged STN β episodes are pathological in parkinsonism and can be used as optimal trigger for future adaptive DBS applications. © 2018 International Parkinson and Movement Disorder Society
Movement disorder society criteria for clinically established early Parkinson's disease
Authors: Berg Daniela , Adler Charles H. , Bloem Bastiaan R. , Chan Piu , Gasser Thomas , Goetz Christopher G. , Halliday Glenda , Lang Anthony E. , Lewis Simon , Li Yuan , Liepelt‐Scarfone Inga , Litvan Irene , Marek Kenneth , Maetzler Corina , Mi Taomian , Obeso José , Oertel Wolfgang , Olanow C. Warren , Poewe Werner , Rios‐Romenets Silvia , Schäffer Eva , Seppi Klaus , Heim Beatrice , Slow Elizabeth , Stern Matthew , Bledsoe Ian O. , Deuschl Günther , Postuma Ronald B.
Published: August 2018

Background: In 2015, the International Parkinson and Movement Disorder Society published clinical diagnostic criteria for Parkinson's disease (PD). Although recent validation studies suggest high accuracy, one unmet need is for highly specific criteria for clinical trials in early/de novo PD.

Objectives: The objective of this study was to generate and test a PD diagnostic criteria termed “clinically established early PD.”

Methods: We modified the Movement Disorder Society criteria to increase specificity for early PD by removing all disease duration components and changing red flags to absolute exclusions. We then estimated the sensitivity/specificity of clinically established early PD criteria in patients with disease duration <5 years, selected from a 626‐patient validation study.

Results: After documentation of parkinsonism, 18 individual exclusion criteria are assessed that preclude the diagnosis of “clinically established early PD.” Among 212 PD and 152 non‐PD patients, the estimated specificity was 95.4%, with 69.8% sensitivity.

Conclusions: We describe high‐specificity criteria for de novo PD, which are freely available for use in clinical trials. © 2018 International Parkinson and Movement Disorder Society
Occupational stress and risk for Parkinson's disease: A nationwide cohort study
Authors: Sieurin Johanna , Andel Ross , Tillander Annika , Valdes Elise G. , Pedersen Nancy L. , Wirdefeldt Karin
Published: August 2018

Background: Stress has been suggested as a contributing factor in the etiology of Parkinson's Disease (PD), but epidemiological evidence is sparse.

Objective: The objective of this study was to explore the association between occupational stress according to the job demands‐control model and the risk for PD.

Methods: We conducted a population‐based cohort study with 2,544,748 Swedes born 1920 to 1950 who had an occupation reported in the population and housing censuses in 1980 or, if missing, in 1970. Job demands and control were measured using a job‐exposure matrix. Incident PD cases were identified using Swedish national health registers from 1987 to 2010. Data were analyzed with Cox regression with age as the underlying time scale, adjusting for sex, education, and chronic obstructive pulmonary disease as a proxy for smoking.

Results: During a mean follow‐up time of 21.3 years, 21,544 incident PD cases were identified. High demands were associated with increased PD risk among men, most evident in men with high education. High control was associated with increased PD risk among the low educated. This association was more pronounced in women. High‐strain jobs (high demands and low control) was only associated with increased PDrisk among men with high education, whereas active jobs (high demands and high control) were associated with increased PD risk among men with low education.

Interpretation: High job demands appear to increase PD risk in men, especially in men with high education, whereas high job control increases PD risk among low educated, more strongly in women. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
HPCA confirmed as a genetic cause of DYT2‐like dystonia phenotype
Authors: Atasu Burcu , Hanagasi Hasmet , Bilgic Basar , Pak Meltem , Erginel‐Unaltuna Nihan , Hauser Ann‐Kathrin , Guven Gamze , Simón‐Sánchez Javier , Heutink Peter , Gasser Thomas , Lohmann Ebba
Published: August 2018

Background: HPCA (hippocalcin) is one of the underlying genetic causes of autosomal‐recessively inherited forms of dystonia. Here, we describe two consanguineous Turkish DYT‐HPCA families carrying the novel HPCA mutations.

Methods: After detailed clinical and neurological examination, whole‐exome sequencing was performed.

Results: Whole‐exome sequencing analysis revealed two homozygous novel truncating mutations (p.W103* and p.P10PfsTer80) in the HPCA gene in two unrelated Turkish dystonia families presenting with complex dystonia.

Conclusions: After identification of HPCA as a genetic cause of DYT‐HPCA‐like dystonia by Charlesworth et al, this is the second report in the scientific literature that describes dystonia families harboring HPCA mutations. Our findings confirm that HPCA leads to recessively inherited dystonia. © 2018 International Parkinson and Movement Disorder Society
Projections of prevalence, lifetime risk, and life expectancy of Parkinson's disease (2010‐2030) in France
Authors: Wanneveich Mathilde , Moisan Frédéric , Jacqmin‐Gadda Hélène , Elbaz Alexis , Joly Pierre
Published: August 2018

Background: Previous studies on the number of Parkinson's disease (PD) patients in the future based on projections of population size underestimated PD burden because they did not take into account the improvement of life expectancy over time.

Objective: The objective of this study was to assess PD progression from 2010 to 2030 in France in terms of prevalent patient numbers, prevalence rates, lifetime risk, and life expectancy with PD, accounting for projections of overall mortality and increased risk of death of PD patients.

Methods: To provide projections of PD burden, we applied a multistate approach considering age and calendar time to incidence and prevalence rates of PD (France 2010) based on drug claims and national demographic data.

Results: The number of PD patients will increase by ∼65% between 2010 (n = 155,000) and 2030 (n ∼ 260,000), mainly for individuals older than 65 years; the prevalence rate of PD after age 45 will increase from 0.59% in 2010 to ∼0.80% in 2030. We project an extension of ∼3 years of the life expectancy of PD patients at 65 years between 2010 (women, 14.8 years; men, 13.0 years) and 2030 (women, 17.8 years; men, 16.1 years), and a relative increase of about 10% of the lifetime risk of PD at 45 years between 2010 (women, 5.5%; men, 6.0%) and 2030 (women, 6.3%; men, 7.4%).

Conclusions: The number of PD patients is predicted to grow substantially in future years as a consequence of population aging and life expectancy improvement. The assessment of the future PD burden is an important step for planning resources needed for patient care in aging societies. © 2018 International Parkinson and Movement Disorder Society
Lactobacillus plantarum C29‐Fermented Soybean (DW2009) Alleviates Memory Impairment in 5XFAD Transgenic Mice by Regulating Microglia Activation and Gut Microbiota Composition
Authors: Lee Hae‐Ji , Hwang Yun‐Ha , Kim Dong‐Hyun
Published: August 2018

Scope

The study aims to determine whether Lactobacillus plantarum C29‐fermented defatted soybean (FDS, DW2009) can attenuate memory impairment in 5XFAD transgenic (Tg) mice.

Methods and results

Oral administration of FDS or C29 increases cognitive function in Tg mice in passive avoidance, Y‐maze, novel object recognition, and Morris water maze tasks. FDS or C29 treatment significantly suppresses amyloid‐β, β/γ‐secretases, caspase‐3 expression, and NF‐κB activation, and activates microglia and apoptotic neuron cell populations, and increases BDNF expression in the brain. FDS or C29 treatment suppresses blood and fecal lipopolysaccharide levels and Enterobacteriaceae population and increases lactobacilli/bifidobacteria populations.

Conclusion

FDS and C29 alleviates the decrease in cognitive function and inhibited amyloid‐β expression in Tg mice by regulating microglia activation and gut microbiota composition.
A more fine‐grained complexity analysis of finding the most vital edges for undirected shortest paths
Authors: Bazgan Cristina , Fluschnik Till , Nichterlein André , Niedermeier Rolf , Stahlberg Maximilian
Published: August 2018

We study the NP‐hard shortest path most vital edges problem arising in the context of analyzing network robustness. For an undirected graph with positive integer edge lengths and two designated vertices s and t, the goal is to delete as few edges as possible in order to increase the length of the (new) shortest st‐path as much as possible. This scenario has been studied from the viewpoint of parameterized complexity and approximation algorithms. We contribute to this line of research by providing refined computational tractability as well as hardness results. We achieve this by a systematic investigation of various problem‐specific parameters and their influence on the computational complexity. Charting the border between tractability and intractability, we also identify numerous challenges for future research.
Alterations in honey bee gut microorganisms caused by Nosema spp. and pest control methods
Authors: Diaz Tsiri , del‐Val Ek , Ayala Ricardo , Larsen John
Published: August 2018

BACKGROUND

Honey bees are associated with gut microorganisms essential for their nutrition and health. The composition of the microbial community can be used as a biological health indicator and is characterized using biomarker fatty acids. Commonly, gut microorganisms are exposed to pathogens and to an array of chemical and biological pest control methods.

RESULTS

We found a strong negative effect on microbial gut community composition when exposed to the bee pest control chemicals oxytetracycline, oxalic acid and imidacloprid, and when inoculated with the bee pest Nosema spp. and the potential bee pest biocontrol agent Lactobacillus plantarum. Results from the in vitro test with bee pest chemicals showed a differential response of Lactobacillus spp. At the community level, some taxonomic groups were more affected depending on treatment, but sharp changes in the microbial structure were caused by compounds generally considered as bee safe.

CONCLUSION

Our results show that pests such as Nosema spp. and pest control methods alter the composition of bee gut microorganisms, which may have severe consequences for pathogen defense, physiology and general honey bee health. In addition, L. plantarum has potential as a biocontrol agent against Nosema spp. © 2018 Society of Chemical Industry
Hierarchical 3D All‐Carbon Composite Structure Modified with N‐Doped Graphene Quantum Dots for High‐Performance Flexible Supercapacitors
Authors: Li Zhen , Liu Xiang , Wang Liang , Bu Fan , Wei Junjie , Pan Dengyu , Wu Minghong
Published: August 2018

Flexible supercapacitors have shown enormous potential for portable electronic devices. Herein, hierarchical 3D all‐carbon electrode materials are prepared by assembling N‐doped graphene quantum dots (N‐GQDs) on carbonized MOF materials (cZIF‐8) interweaved with carbon nanotubes (CNTs) for flexible all‐solid‐state supercapacitors. In this ternary electrode, cZIF‐8 provides a large accessible surface area, CNTs act as the electrical conductive network, and N‐GQDs serve as highly pseudocapactive materials. Due to the synergistic effect and hierarchical assembly of these components, N‐GQD@cZIF‐8/CNT electrodes exhibit a high specific capacitance of 540 F g−1 at 0.5 A g−1 in a 1 m H2SO4 electrolyte and excellent cycle stability with 90.9% capacity retention over 8000 cycles. The assembled supercapacitor possesses an energy density of 18.75 Wh kg−1 with a power density of 108.7 W kg−1. Meanwhile, three supercapacitors connected in series can power light‐emitting diodes for 20 min. All‐solid‐state N‐GQD@cZIF‐8/CNT flexible supercapacitor exhibits an energy density of 14 Wh kg−1 with a power density of 89.3 W kg−1, while the capacitance retention after 5000 cycles reaches 82%. This work provides an effective way to construct novel electrode materials with high energy storage density as well as good cycling performance and power density for high‐performance energy storage devices via the rational design.
Peroxisome proliferator‐activated receptor alpha accelerates neuronal differentiation and this might involve the mitogen‐activated protein kinase pathway
Authors: Lin Chingju , Chen Pei‐Yi , Chan Hsu‐Chin , Huang Yi‐Ping , Chang Nai Wen
Published: August 2018

Activation of peroxisome proliferator‐activated receptor alpha (PPARα) has been reported to modulate cell proliferation, migration, and differentiation in astrocytes. In this study, we used a retinoic acid (RA)‐induced differentiation model of NTERA‐2/clone D1 (NT2) cells to explore the functional significance of PPARα in neuronal differentiation. We found that activating PPARα by Wy14643 accelerated neuronal differentiation via regulating the expression of neuronal markers. RT‐PCR assays showed a significant increase in NeuroD expression and a decrease in nestin expression in cells treated concomitantly with RA and Wy14643 for 2 days compared to the levels in cells treated with RA alone. Expression of MAP2 protein, a mature neuronal marker, was markedly upregulated at day 10 of Wy14643 treatment, which was maintained after 21 days of neuronal formation. Corresponding to the changes in MAP2 expression, the expression of Cdk5 was upregulated with Wy14643 exposure from day 10 to day 21. Moreover, cells treated with Wy14643 displayed higher expression levels of phospho‐ERK and phospho‐p38 in the differentiation process than cell treated with RA alone. These results indicated that activation of PPARα accelerated neuronal differentiation through upregulating the expression of NeuroD, MAP2, and Cdk5 and downregulating the expression of nestin. MAPK signals, ERK and p38, might contribute to the accelerated differentiation process. These findings suggest that PPARα plays a role in regulating neuronal differentiation and may be beneficial for functional recovery from neurological disorders.
Gender Identity, and Equality and Non-discrimination of Same Sex Couples
Authors: Carrillo-Santarelli Nicolás
Published: August 2018

In its advisory opinion, OC-24/17 (Advisory Opinion), the Inter-American Court of Human Rights (IACtHR or Court) addressed globally debated issues concerning gender identity, same-sex relationships, and the rights of LGBTI persons. As discussed below, the Court reached conclusions more progressive than those of its European counterpart, due to its finding that the principle of individual autonomy is embedded in the foundations of human rights law and permeates individual self-determination, the free development of one's personality, and the protection of different models of the family. In line with an apparent trend in the Court's case law, the Advisory Opinion rejects the idea that domestic societies are sometimes entitled, by virtue of a margin of appreciation, to choose among different possibilities for protecting human rights, provided that certain international legal limits are observed—an idea addressed in the dissenting opinion.
Understanding the Challenges, Yet Focusing on the Successes: An Investigation into Indigenous University Students’ Academic Success
Authors: Lydster Cameron , Murray Jason
Published: August 2018

This paper reports on experiences of Indigenous students and staff involved in Bond Indigenous Tutoring (BIT). It aimed to gain insight regarding topics including challenges faced by Indigenous students, why some students discontinued their studies, and concepts of success at university. Findings revealed the main challenges included the transition from secondary to tertiary education and not being prepared academically. BIT staff identified family responsibilities and being dislocated from kinship networks as challenges, while students stated these were factors explaining why Indigenous students discontinued their studies. A whole of university approach was found to be required to effectively support Indigenous students. Success was defined as more than Grade Point Average, as it entailed being able to enjoy future endeavours. This paper contributes to the evidence that tuition programmes and Indigenous centres at university are key contributors to success, and it is argued that such success must become the norm as opposed to the exception.
The sensitivity of sensitivity analysis
Authors: Plümper Thomas , Traunmüller Richard
Published: August 2018

This article evaluates the reliability of sensitivity tests. Using Monte Carlo methods we show that, first, the definition of robustness exerts a large influence on the robustness of variables. Second and more importantly, our results also demonstrate that inferences based on sensitivity tests are most likely to be valid if determinants and confounders are almost uncorrelated and if the variables included in the true model exert a strong influence on outcomes. Third, no definition of robustness reliably avoids both false positives and false negatives. We find that for a wide variety of data-generating processes, rarely used definitions of robustness perform better than the frequently used model averaging rule suggested by Sala-i-Martin. Fourth, our results also suggest that Leamer’s extreme bounds analysis and Bayesian model averaging are extremely unlikely to generate false positives. Thus, if based on these inferential criteria a variable is robust, it is almost certain to belong into the empirical model. Fifth and finally, we also show that researchers should avoid drawing inferences based on lack of robustness.
Associations of plasma very-long-chain SFA and the metabolic syndrome in adults
Authors: Zhao Jing , Li Xiaofan , Li Xiang , Chu Qianqian , Zhou Yunhua , Li Zi , Zhang Hong , Brenna Thomas J. , Song Yiqing , Gao Ying
Published: August 2018

Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (allPfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3,n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms.
Beyond Opportunity Costs: Campaign Messages, Anger and Turnout among the Unemployed
Authors: Aytaç S. Erdem , Rau Eli Gavin , Stokes Susan
Published: August 2018

Are people under economic stress more or less likely to vote, and why? With large observational datasets and a survey experiment involving unemployed Americans, we show that unemployment depresses participation. But it does so more powerfully when the unemployment rate is low, less powerfully when it is high. Whereas earlier studies have explained lower turnout among the unemployed by stressing the especially high opportunity costs these would-be voters face, our evidence points to the psychological effects of unemployment and of campaign messages about it. When unemployment is high, challengers have an incentive to blame the incumbent, thus eliciting anger among the unemployed. Psychologists have shown anger to be an approach or mobilizing emotion. When joblessness is low, campaigns tend to ignore it. The jobless thus remain in states of depression and self-blame, which are demobilizing emotions.
Microbiological characterisation and impact of suspended solids on pathogen removal from wastewaters in dairy processing factories
Authors: Fitzhenry Kelly , Rowan Neil , Finnegan William , Zhan Xinmin , Clifford Eoghan
Published: August 2018

In this Research Communication we investigate the microbiological profile of 12 dairy wastewater streams from three contrasting Irish dairy processing factories to determine whether faecal indicators/pathogens were present and in turn, whether disinfection may be required for potential water reuse within the factory. Subsequently, the impact of suspended solids on the inactivation efficiency of Escherichia coli via two means of ultravoilet (UV) disinfection; flow-through pulsed UV (PUV) and continuous low pressure UV (LPUV) disinfection was analysed. Faecal indicators total coliforms and E. coli were detected in 10 out of the 12 samples collected at the dairy processing factories while pathogenic bacteria Listeria monocytogenes was detected in all samples collected at 2 out of the 3 factories. Salmonella spp. was undetected in all samples. The results also indicated that organic dairy wastewater solids had an impact on the performance efficiency of the PUV system and, to a lesser extent, the LPUV system. The findings indicate that the targeting of key pathogens would be required to enable wastewater reuse (and indeed effluent discharges if regulation continues to become more stringent) and that LPUV may offer a more robust disinfection method as it appears to be less susceptible to the presence of suspended solids.