bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and ex vivo analyses of amyloid toxicity in the Tc1 mouse model of Down syndrome
Authors: Naert Gaëlle , Ferré Valentine , Keller Emeline , Slender Amy , Gibbins Dorota , Fisher Elizabeth MC , Tybulewicz Victor LJ , Maurice Tangui
Published: December 2017

Rationale:

The prevalence of Alzheimer’s disease is increased in people with Down syndrome. The pathology appears much earlier than in the general population, suggesting a predisposition to develop Alzheimer’s disease. Down syndrome results from trisomy of human chromosome 21, leading to overexpression of possible Alzheimer’s disease candidate genes, such as amyloid precursor protein gene. To better understand how the Down syndrome context results in increased vulnerability to Alzheimer’s disease, we analysed amyloid-β [25-35] peptide toxicity in the Tc1 mouse model of Down syndrome, in which ~75% of protein coding genes are functionally trisomic but, importantly, not amyloid precursor protein.

Results:

Intracerebroventricular injection of oligomeric amyloid-β [25-35] peptide in three-month-old wildtype mice induced learning deficits, oxidative stress, synaptic marker alterations, activation of glycogen synthase kinase-3β, inhibition of protein kinase B (AKT), and apoptotic pathways as compared to scrambled peptide-treated wildtype mice. Scrambled peptide-treated Tc1 mice presented high levels of toxicity markers as compared to wildtype mice. Amyloid-β [25-35] peptide injection in Tc1 mice induced significant learning deficits and enhanced glycogen synthase kinase-3β activity in the cortex and expression of apoptotic markers in the hippocampus and cortex. Interestingly, several markers, including oxidative stress, synaptic markers, glycogen synthase kinase-3β activity in the hippocampus and AKT activity in the hippocampus and cortex, were unaffected by amyloid-β [25-35] peptide injection in Tc1 mice.

Conclusions:

Tc1 mice present several toxicity markers similar to those observed in amyloid-β [25-35] peptide-treated wildtype mice, suggesting that developmental modifications in these mice modify their response to amyloid peptide. However, amyloid toxicity led to severe memory deficits in this Down syndrome mouse model.
A Note on the Use of Identification Jacobians for Robot Calibration
Authors: Zhuang Hanqi
Published: December 2017

Two issues related to robot calibration are addressed in this communication. The first issue is how many position-dependent error parameters should be used in modeling a robot manipulator. The second issue is how to select a proper identification Jacobian when only position measurements of the robot end effector are available. Conclusions are made regarding these issues after short discussions.
Enhanced interfacial adhesion of UHMWPE fibers by alkali treatment and its behavior to PI resins
Authors: Tang Gang , Hu Xiong , Tang Tianhao , Claramunt Christophe , Liu Chengliang
Published: December 2017

The effect of alkali treatment on the UHMWPE fiber and interface of its composites was evaluated by atomic force microscopy, X-ray photoelectron spectroscopy, single-fiber tensile strength analysis, and dynamic contact angle analysis. The objective of this work is to improve the interlaminar shear strength of the composites by mixing the PI resin and modifying the UHMWPE fibers. Surface analysis showed that after treatment, the surface roughness and the wetting ability of UHMWPE fiber were increased. Results indicated that the alkali treatment plays a more important role in improving the surface property and interfacial adhesion of UHMWPE fibers’ composites.
Thermal decomposition kinetic study of multiwalled carbon nanotube buckypaper-reinforced poly(ether-imide) composites
Authors: Ribeiro Bruno , Santos LFP , Santos AL , Costa ML , Botelho EC
Published: December 2017

Poly(ether-imide) (PEI)-based composites filled with multiwalled carbon nanotubes in a dispersed form (1.0 wt%) and as buckypaper (BP) (25 wt%) have been prepared by mixing solution and hot compression molding technique, respectively. Vacuum filtration technique with the aid of water-based surfactant Triton X-100 was employed to produce BP sheets. The thermal stability of the composites was evaluated by thermogravimetric analysis and revealed a strong increase in thermal degradation temperature when BPs were used as nanofiller. Ozawa–Wall–Flyn model was used to determine the kinetic parameters. It was observed an increase in activation energy as the nanotubes concentration rise, suggesting the formation of more thermally stable systems. In addition, half-life time as function of temperature demonstrated that BP-based composites could operate for 3200 years at 200°C. These results concluded that carbon nanotube BP could contribute to improve significantly the thermal stability of PEI matrix.
Preparation, bioactivity, and cytotoxicity studies of poly(ester urethane)s/SiO2 nanocomposites
Authors: Jiménez-Gallegos Rodrigo , Rodríguez-Lorenzo Luis M , San Roman Julio , Téllez-Jurado Lucía
Published: December 2017

Degradable poly(ester urethane)s (PEUS)/nanosilica composites are prepared, and a preliminary evaluation of their potential to be used in calcified tissue regeneration is performed. First, poly(ethylene glycol succinate) (PEGS) of different molecular weights is prepared and then a prepolymer with an excess of 1,6-hexamethylene diisocyanate is synthesized; this prepolymer is subsequently extended with 1,4-butanediol in the presence of nanosilica particles. The effects of the structures of PEGS and PEUS are studied by means of attenuated total reflectance infrared, gel permeation chromatography, X-ray diffraction, thermogravimetric analysis, optical microscopy, and scanning electron microscopy. The materials show that similar crystalline structure independently of the molecular weight, however, increases the thermal resistance with higher molecular weight of nanocomposites. After soaking in simulated body fluid, the appearance of apatite phosphate bands in Fourier transformed infrared spectra suggests the bioactive character of these composites. In addition, degradation and toxicity test are performed. The materials are degradable but not cytotoxic after 7 days of testing.
Researching Collective Bargaining Agreements: Building Conceptual Understanding in an Era of Declining Union Power
Authors: Osborne-Lampkin La’Tara , Cohen-Vogel Lora , Feng Li , Wilson Jerry J.
Published: December 2017

Here, we examine over two decades of empirical literature to explore the ways scholars have been working to reveal the changing set of policy and political conditions in which teachers unions are operating. In this context, we identify the conceptual models educational researchers have used to frame their research and the applications of these frameworks in the literature on teachers unions. Our findings reveal that the research on teachers unions over the past two decades provides deep historical context. Less evident in this research are explicit conceptual groundings to theory and how the theoretical/empirical literature is applied in inquiry.
Exploring Perceived Barriers to Medication Adherence and the Use of Mobile Technology in Underserved Patients With Chronic Conditions
Authors: Hincapie Ana L. , Gupta Vasudha , Brown Stephenne A. , Metzger Anne H.
Published: December 2017

Background and Objective:

Evidence suggests that the prevalence of medication nonadherence is greater in medically underserved, low-income communities. There is paucity of qualitative data examining the potential use of mobile health (mHealth) in underserved patients. This study aimed to explore barriers to medication adherence and identify opportunities and challenges for the potential use of mHealth adherence interventions in an underserved population.

Methods:

A qualitative cross-sectional focus group was conducted. Focus groups were conducted with underserved patients recruited at a federally qualified health center. The Health Belief Model was used as theoretical framework to develop the focus group guide. Audio-recorded data were transcribed and thematically analyzed to identify common themes across the data set.

Results:

Seventeen patients participated in 4 focus groups. Findings were organized by the following themes: (1) perceived barriers to medication adherence, (2) everyday practices used to improve medication adherence, and (3) perceived benefits and barriers to technology use. Use of text messages seemed beneficial; however, not carrying a phone always was a significant barrier for patients. Some patients expressed willingness to try smartphone applications but stated that they would not be able to afford them. Changes in daily routine and complexity of medication regimens were seen as barriers to medication adherence.

Conclusions:

Findings underscore the importance of considering diverse experiences when engaging patients in mHealth for medication adherence. Providing patient-centered approaches to assist patients construct their individualized medication adherence strategies may lead to better outcomes.
Graspable Objects Grab Attention More Than Images Do
Authors: Gomez Michael A. , Skiba Rafal M. , Snow Jacqueline C.
Published: December 2017

The opportunity an object presents for action is known as an affordance. A basic assumption in previous research was that images of objects, which do not afford physical action, elicit effects on attention and behavior comparable with those of real-world tangible objects. Using a flanker task, we compared interference effects between real graspable objects and matched 2-D or 3-D images of the items. Compared with both 2-D and 3-D images, real objects yielded slower response times overall and elicited greater flanker interference effects. When the real objects were positioned out of reach or behind a transparent barrier, the pattern of response times and interference effects was comparable with that for 2-D images. Graspable objects exert a more powerful influence on attention and manual responses than images because of the affordances they offer for manual interaction. These results raise questions about whether images are suitable proxies for real objects in psychological research.
A 5500-year oxygen isotope record of high arctic environmental change from southern Spitsbergen
Authors: Arppe Laura , Kurki Eija , Wooller Matthew J , Luoto Tomi P , Zajączkowski Marek , Ojala Antti EK
Published: December 2017

The oxygen isotope composition of chironomid head capsules in a sediment core spanning the past 5500 years from Lake Svartvatnet in southern Spitsbergen was used to reconstruct the oxygen isotope composition of lake water (δ18Olw) and local precipitation. The δ18Olw values display shifts from the baseline variability consistent with the timing of recognized historical climatic episodes, such as the Roman Warm Period, the Dark Ages Cold Period and the ‘Little Ice Age’. The highest values of the record, ca. 3‰ above modern δ18Olw values, occur at ca. 1900–1800 cal. yr BP. Three negative excursions increasing in intensity toward the present, at 3400–3200, 1250–1100, and 350–50 cal. yr BP, are tentatively linked to roughly synchronous episodes of increased glacier activity and general cold spells around the northern North Atlantic. Their manifestation in the Svartvatnet δ18Olw record not only testify to the sensitivity and potential of high Arctic lacustrine δ18Ochir records in tracking terrestrial climate evolution but also highlight nonlinear dynamics within the northern North Atlantic hydroclimatic system. The ‘Little Ice Age’ period at 350–50 cal. yr BP displays a remarkable 8–9‰ drop in δ18Olw values, construed to predominantly represent significantly decreased winter temperatures during a period of increased seasonal differences and extended sea ice cover inducing changes in moisture source regions.
Surface water productivity and sediment transport by Bering Strait throughflow in the Chukchi Shelf (the western Arctic Ocean) during the Holocene
Authors: Khim Boo-Keun , Lee Mi Jung , Cho Hyen Goo , Park Kwangkyu
Published: December 2017

Diverse paleoceanographic proxies from three sediment cores (GC12ex, JPC35, and JPC30) collected from the Chukchi Shelf north of the Bering Strait elucidate the Holocene paleoceanographic changes (surface water productivity and sediment transport) caused by the Bering Strait throughflow from the Bering Sea into the Chukchi Sea. Lithology of three sediment cores identified the same three units. Based on comparison and correlation to adjacent age-dated cores as well as AMS 14C dates of core GC12ex, the boundary between Unit 1 and Unit 2a is dated about 8500 cal. yr BP, and the boundary between Unit 2a and Unit 2b is also dated about 4500 cal. yr BP. Consistent down-core profiles of the geochemical and isotopic properties among the three cores differentiate the paleoceanographic conditions corresponding to lithologic units. Based on the biogenic opal, total organic carbon, and δ13C values, Unit 1 is characterized by low surface water marine productivity under relatively shallow water with weak transport of Bering Strait throughflow. Unit 2a shows a mixture of terrestrial and marine contributions, indicating the onset of increased marine surface water productivity after the main flooding (~11,500 cal. yr BP) of the Bering Strait by the Holocene sea-level rise. Unit 2b exhibits stable and enhanced marine biogenic opal production similar to the present-day oceanographic conditions. Such paleoceanographic changes were confirmed by the clay minerals (smectite, illite, kaolinite, and chlorite) and detrital isotopes (εNd and 87Sr/86Sr). Thus, the Bering Strait throughflow played an important role on surface water productivity and sediment deposition in the Chukchi Shelf in response to Holocene sea-level rise after the opening of the Bering Strait.
Attitude Moralization: Probably Not Intuitive or Rooted in Perceptions of Harm
Authors: Skitka Linda J. , Wisneski Daniel C. , Brandt Mark J.
Published: December 2017

People vary in the extent to which they imbue attitudes with moral conviction, and this variation is consequential. Yet we know relatively little about what makes people’s feelings about a given attitude object transform from a relatively nonmoral preference to a moral conviction. In this article, we review evidence from two experiments and a field study that sheds some light on the processes that lead to attitude moralization. This research explored the roles of incidental and integral affect, cognitive factors such as recognition of harm, and whether attitude-moralization processes can occur outside conscious awareness or require some level of conscious deliberation. The findings present some challenges to contemporary theories that emphasize the roles of intuition and harm and indicate that more research designed to better understand moralization processes is needed.
Palliative Care Providers’ Practices Surrounding Psychological Distress Screening and Treatment: A National Survey
Authors: Kozlov Elissa , Eghan Claude , Moran Sheila , Herr Keela , Reid M. Carrington
Published: December 2017

Objective:

To investigate how inpatient palliative care teams nationwide currently screen for and treat psychological distress.

Methods:

A web-based survey was sent to inpatient palliative care providers of all disciplines nationwide asking about their practice patterns regarding psychological assessment and treatment. Descriptive statistics were used to characterize the sample and responses, and analysis of variance was conducted to determine whether certain disciplines were more likely to utilize specific treatment modalities.

Results:

A total of N = 236 respondents were included in the final analyses. Providers reported that they encounter psychological distress regularly in their practice and that they screen for distress using multiple methods. When psychological distress is detected, providers reported referring patients to an average of 3 different providers (standard deviation = 1.46), most frequently a social worker (69.6%) or chaplain (65.3%) on the palliative care team. A total of 84.6% of physicians and 54.5% of nurse practitioners reported that they prescribe anxiolytics or selective serotonin reuptake inhibitors to patients experiencing psychological distress.

Discussion and Conclusions:

This study revealed significant variability and redundancy in how palliative care teams currently manage psychological distress. The lack of consistency potentially stems from the variability in the composition of palliative care teams across care settings and the lack of scientific evidence for best practices in psychological care in palliative care. Future research is needed to establish best practices in the screening and treatment of psychological distress for patients receiving palliative care.
Recognition of indigenous and foreign speech in a noisy classroom: A case of primary school pupils
Authors: Uguru Joy O , Beerends John G , Ebem Deborah
Published: December 2017

This study examines the level of speech recognition of English and Igbo utterances by 70 grade four children. The children, whose mother tongue is Igbo and aged between 8 and 10 years, had English monosyllabic words as well as Igbo monosyllabic and disyllabic words dictated to them in noisy and quiet classrooms. The results show that in noise, their level of recognition was significantly higher for English utterances (p < 0.05) while in quiet, it was significantly higher for Igbo (p < 0.05). Thus, the findings confirm those of previous studies that the recognition of Igbo is more affected by noise. In terms of the recognition of phonemes in quiet and noise, for both languages, the ‘t’ test analyses showed significant difference (p < 0.05) in the pupils’ recognition of vowels and consonants in both languages, with vowels being more identified than consonants in both noise and quiet. Hence, though the recognition of both languages is hindered in noise, the study of Igbo requires an acoustically serene environment for maximum results.
The effects of the 2014 World Cup and the 2016 Olympic Games on Brazilian international travel receipts
Authors: Meurer Roberto , Lins Hoyêdo Nunes
Published: December 2017

The authors estimate the effect of hosting the World Cup in 2014 and the Olympic Games in 2016 on Brazilian international travel receipts. Results show that the World Cup generated an increase of about 50% in receipts during the 2 months of the event, while the estimated effect of the Olympics was an increase of about 28% during 1 month. In the month after the events, there was a fall of almost the same amount, and no effect of the previous rise in receipts was detected 2 months after the events. Therefore, these effects were immediate and short-lived.
A three-year national follow-up study on the development of community-level cancer rehabilitation in Denmark
Authors: Kristiansen Maria , Adamsen Lis , Piil Karin , Halvorsen Ida , Nyholm Nanna , Hendriksen Carsten
Published: December 2017

Aims: Scandinavian cancer care policies emphasise community-level rehabilitation services, but little is known about changes in service provision over time. This follow-up study explores development in these services in Danish municipalities, focusing on availability, utilisation and organisation of services, including existing opportunities and challenges. Methods: A national survey among all 98 Danish municipalities was conducted in 2013 (baseline) and repeated in 2016 (follow-up). The electronic questionnaire comprised closed- and open-ended questions. Data were analysed using descriptive statistics and content analysis. Results: A total of 93 municipalities responded (95% response rate) and the services offered primarily comprised group physical activity, dietary advice, smoking cessation and individual counselling on physical activity. The number of patients enrolled was below the estimated number needing rehabilitation in Denmark. Inequality in utilisation by ethnicity, age and gender was reported. Key challenges for the delivery of services were: inadequate referral and recruitment procedures; lack of needs assessment tools; obstacles to ensuring collaboration and referral of patients between hospitals and municipalities; and inadequate evidence on the rehabilitation’s effect. Key recommendations include ensuring collaboration between municipalities; provision of diagnosis-specific group-based activities; services focusing on physical activity; and gender-specific activities directed particularly at men. Conclusions: This study, which highlights improvements in the provision of community-level cancer rehabilitation, recommends that more effort be made to ensure equality in utilisation across patient groups, improved integration of municipal-level services into cancer care trajectories, more uniform documentation of service delivery and the enforcement of patient outcomes to gradually build a more robust evidence base for community-level cancer rehabilitation.
Introduction: Toward Hybrid Media Events of Terrorist Violence
Authors: Sumiala Johanna Maaria , Valaskivi Katja
Published: December 2017

This is an introdcution to a special section in the journal in which we examine terrorism as a media event. The introduction reviews the classic works by Elihu Katz and Daniel and adds our own contemporary extension of their theories. It acknowledges the significance of temporality and related mnemonic patterns (Zelizer, Kraidy, in this introduction); networked, relational territorialities (Kraidy, in this introduction); and the discursive politics applied to categorize the violence in question (Hervik; Cui and Rothenbuhler; Price, in this introduction), but it also suggests a more detailed focus on the hybrid dynamics between actors, platforms, and messages which circulate during violent media events. The authors continue the debate on the complex relationship between media, event, and terror by introducing hybridity as yet another angle to this topical discussion.
A simple and fast method to image calcium activity of neurons from intact dorsal root ganglia using fluorescent chemical Ca2+ indicators
Authors: Chen Yong , Huang Li-Yen M
Published: December 2017

Chemical calcium indicators have been commonly used to monitor calcium (Ca2+) activity in cell bodies, i.e., somata, of isolated dorsal root ganglion neurons. Recent studies have shown that dorsal root ganglion somata play an essential role in soma–glia interactions and actively participate in the transmission of nociceptive signals. It is therefore desirable to develop methods to study Ca2+ activity in neurons and glia in intact dorsal root ganglia. In our previous studies, we found that incubation of intact dorsal root ganglia with acetoxymethyl dye resulted in efficient Ca2+ dye loading into glial cells but limited dye loading into neurons. Here, we introduce a useful method to load Ca2+ dyes in intact dorsal root ganglion neurons through electroporation. We found that electroporation greatly facilitated loading of Fluo-4 acetoxymethyl, Oregon green bapta-1-488 acetoxymethyl, and Fluo-4 pentapotassium salt into dorsal root ganglion neurons. In contrast, electroporation did not further facilitate dye loading into glia. Using electroporation followed by incubation of acetoxymethyl form Ca2+ dye, we can load acetoxymethyl Ca2+ dye well in both neurons and glia. With this approach, we found that inflammation induced by complete Freund’s adjuvant significantly increased the incidence of neuron–glia interactions in dorsal root ganglia. We also confirmed the actions of capsaicin and morphine on Ca2+ responses in dorsal root ganglion neurons. Thus, by promoting the loading of Ca2+ dye in neurons and glia through electroporation and incubation, Ca2+ activities in neurons and neuron–glia interactions can be well studied in intact dorsal root ganglia.
Are morbidity and mortality case review practices in Scottish intensive care units aligned to national standards?
Authors: Al-Haddad Mohammed(Mo) Faik , Cadamy Andrew , Black Euan , Slade Kate
Published: December 2017

Introduction

Both Scottish and UK standards guidelines recommend that intensive care units should hold regular, structured, multidisciplinary morbidity and mortality meetings. The aim of this survey was to ascertain the nature of current practice with regards to morbidity and mortality case reviews and meetings in all intensive care units in Scotland.

Methods

Semi-structured telephone interviews were conducted with a consultant from all Scottish intensive care units. A list of intensive care units in Scotland was obtained from the Scottish Intensive Care Society Audit Group annual report.

Results

All 24 intensive care units (100%) in Scotland were surveyed. The interviews took an average of 20 min. The three cardiac intensive care units were excluded from analysis. All other intensive care units had morbidity and mortality meetings and 18 units had a morbidity and mortality clinical lead. Nineteen intensive care units held joint morbidity and mortality meetings, eight of which were regular. In all intensive care units, meetings were attended by consultants and trainees. In 14 intensive care units, meetings were attended by nurses, seven by allied health professionals, 1 by a manager and 11 by other professionals. All mortality cases in intensive care unit were discussed in 19 intensive care units, in the other two intensive care units, 10–20% of mortality cases were discussed.

Conclusion

There is a wide variation in the processes of reviewing mortality cases and significant events in intensive care units across Scotland, and in the way morbidity and mortality meetings are organised and held. Based on this survey, there is scope for improving the consistency of approach to morbidity and mortality case reviews and meetings in order to improve education and facilitate shared learning.
Advanced finite element cross-country ski boot model for mass optimization directions considering flexion stiffness
Authors: Hladnik Jurij , Jerman Boris
Published: December 2017

Flexion stiffness and mass were recognized as two important parameters of energy efficiency for modern top-class ski boots used in skate cross-country skiing. This article summarizes the study on mass optimization of the front foot region of an existing cross-country ski boot, while considering its flexion stiffness. For this purpose, a finite element model of the boot and an artificial foot for simulation of boot flexion stiffness measurement were made. The boot consists of textiles which require specific measurements for their characterization and special finite element material models for their realization. The finite element model was validated through a three-step validation process, in which flexion stiffness of the complete and stripped versions of the finite element model were compared with experimentally acquired flexion stiffness. Flexion stiffness contributions of individual boot components of the front foot region were acquired from the strain energy accumulated in their finite element. Using flexion stiffness and mass contributions and ratios between them (flexion stiffness to mass contributions), directions for flexion stiffness to mass contribution optimization of the boot’s front region were determined. The shoe-upper and shoe-cap were the most efficient regarding their flexion stiffness to mass contribution ratios and were suggested to be thickened. The soles had the highest potential for the boot’s flexion stiffness to mass contribution optimization due to their high mass contribution and relatively low flexion stiffness to mass contribution ratios. As a result, recommendations were made to reduce the soles’ size and/or increase their flexion stiffness to mass contribution ratios. These recommendations are similar to recommendations from a previous study, despite the higher finite element model accuracy and different method used to determine the flexion stiffness contributions.
Threat in the Company of Men: Ensemble Perception and Threat Evaluations of Groups Varying in Sex Ratio
Authors: Alt Nicholas P. , Goodale Brianna , Lick David J. , Johnson Kerri L.
Published: December 2017

Everyday, we visually perceive people not only in isolation but also in groups. Yet, visual person perception research typically focuses on inferences made about isolated individuals. By integrating social vision and visual ensemble coding, we present novel evidence that (a) perceivers rapidly (500 ms) extract a group’s ratio of men to women and (b) both explicit judgments of threat and indirect evaluative priming of threat increase as the ratio of men to women in a group increases. Furthermore, participants’ estimates of the number of men, and not perceived men’s coalition, mediate the relationship between the ratio of men to women and threat judgments. These findings demonstrate the remarkable efficiency of perceiving a group’s sex ratio and downstream evaluative inferences made from these percepts. Overall, this work advances person perception research into the novel domain of people perception, revealing how the visually perceived sex ratio of groups impacts social judgments.
Wearable step counting using a force myography-based ankle strap
Authors: Chu Kelvin HT , Jiang Xianta , Menon Carlo
Published: December 2017

Introduction

Step counting can be used to estimate the activity level of people in daily life; however, commercially available accelerometer-based step counters have shown inaccuracies in detection of low-speed walking steps (<2.2 km/h), and thus are not suitable for older adults who usually walk at low speeds. This proof-of-concept study explores the feasibility of using force myography recorded at the ankle to detect low-speed steps.

Methods

Eight young healthy participants walked on a treadmill at three speeds (1, 1.5, and 2.0 km/h) while their force myography signals were recorded at the ankle using a customized strap embedded with an array of eight force-sensing resistors. A K-nearest neighbour model was trained and tested with the recorded data. Additional three mainstream machine learning algorithms were also employed to evaluate the performance of force myography band as a pedometer.

Results

Results showed a low error rate of the step detection (<1.5%) at all three walking speeds.

Conclusions

This study demonstrates not only the feasibility of the proposed approach but also the potential of the investigated technology to reliably monitor low-speed step counting.
Estimation of individual thigh muscle volumes from a single-slice muscle cross-sectional area and muscle thickness using magnetic resonance imaging in patients with knee osteoarthritis
Authors: Yamauchi Koun , Yoshiko Akito , Suzuki Shigetoshi , Kato Chisato , Akima Hiroshi , Kato Takayuki , Ishida Koji
Published: December 2017

Purpose:

This study aimed to identify the best single-slice anatomical muscle cross-sectional area (CSA) and muscle thickness (MT) on magnetic resonance imaging (MRI) to estimate the overall individual muscle volumes (MVs) of knee extensors and flexors in patients with knee osteoarthritis (KOA).

Methods:

Twelve patients (24 legs; 4 men and 8 women) with KOA underwent a 1.5-Tesla axial MRI scan in the femoral region of interest (ROI), between the lesser trochanter and rectus femoris tendon. Individual MVs were calculated by numerical integration based on individual CSAs analyzed at the ROI. The best slice was determined as follows: coefficient of determination ( R2) between MVs measured and those estimated from the femoral length (FL) × CSAs or FL × MTs measured at each 10% interval level of the ROI. These estimation equations were applied for a cross-validation group (24 KOA patients: 12 men and 12 women).

Results:

Estimated individual MVs of knee extensors and flexors, based on the CSAs at the distal 10% level, significantly correlated with each of the measured individual MVs ( R2: 0.79–0.96, p < 0.05 for all). Similarly, estimated individual knee extensor MVs, based on MTs at the mid-slice, significantly correlated with each of the measured individual MVs ( R2: 0.77–0.84, p < 0.05 for all). The application of the developed regression equation to the cross-validation group did not exhibit any systematic bias.

Conclusion:

These simple methods could be applied in prospective research with a larger number of patients with KOA.
Age Dependence of Thresholds for Speech in Noise in Normal-Hearing Adolescents
Authors: Jacobi Irene , Sheikh Rashid Marya , de Laat Jan A. P. M , Dreschler Wouter A.
Published: December 2017

Previously found effects of age on thresholds for speech reception thresholds in noise in adolescents as measured by an online screening survey require further study in a well-controlled teenage sample. Speech reception thresholds (SRT) of 72 normal-hearing adolescent students were analyzed by means of the online speech-in-noise screening tool Earcheck (In Dutch: Oorcheck). Screening was performed at school and included pure-tone audiometry to ensure normal-hearing thresholds. The students’ ages ranged from 12 to 17 years. A group of young adults was included as a control group. Data were controlled for effects of gender and level of education. SRT scores within the controlled teenage sample revealed an effect of age on the order of an improvement of −0.2 dB per year. Effects of level of education and gender were not significant. Hearing screening tools that are based on SRT for speech in noise should control for an effect of age when assessing adolescents. Based on the present data, a correction factor of −0.2 dB per year between the ages of 12 and 17 is proposed. The proposed age-corrected SRT cut-off scores need to be evaluated in a larger sample including hearing-impaired adolescents.
Exploring Decisions to Undertake a Marathon and Adherence Challenges in a Novice Runner With Parkinson
Authors: Ramaswamy Bhanu , Johnson Christian
Published: December 2017

Evidence endorses the benefits of more vigorous exercise for people with Parkinson's, particularly following diagnosis, yet is not clear which style is optimal. The authors share perspectives and decisions made as a physiotherapist (assisted by a sports and exercise science student) and a novice runner with Parkinson's in his late 50s, respectively. The exercise goal chosen by the runner (the case report participant) to minimize the degenerative effects of the progressive condition was to complete a marathon.

Methods:

This coauthored report evaluates the participant’s progress utilizing physical fitness assessment data plus reflections on his training regime and notes from training diaries for the year before and after the marathon.

Results:

The participant received nutritional advice for weight management as exercise increased and physiotherapy for injuries from mounting activity level on Parkinsonian muscle tone. Fitness and function improved or were maintained (leg power, flexibility, timed functional walking, and balance). Most, however, returned to baseline within 6 months following the marathon as training intensity dropped.

Conclusions:

Physical function can be improved or maintained in individuals with neurodegenerative conditions with correct exercise and nutritional advice. The participant’s choice of running was based on recommendations for condition maintenance and not enjoyment, so adherence and completion of the marathon goal required professional, family, and technological support.
The air of Europe: where are we going?
Authors: Annesi-Maesano Isabella
Published: December 2017

Air pollution constitutes one of the main threats to public health in Europe. Significant impacts on the health of Europeans in terms of morbidity and mortality have been observed, even in cases of low exposure and where pollutant levels are within limits set by the European Union (EU). The respiratory system is a primary target of the harmful effects of key air pollutants. Emissions of many air pollutants have decreased substantially over the past decades in Europe, resulting in diminished concentrations and improved air quality. However, in several European cities concentrations still exceed EU reference values and, more often, the stricter World Health Organization air quality guidelines for all regulated air pollutants (particles with 50% cut-off aerodynamic diameters of 10 and 2.5 µm, nitrogen dioxide (NO2), benzo[a]pyrene and ozone (O3)) except sulfur dioxide. In addition, current trends indicate that in the absence of substantial changes, particulate matter, NO2and O3will still exceed limits in 2020. Additional efforts must be made to comply with current standards and guidelines. These should include a more accurate and detailed monitoring of air pollutants, reduction of emissions and individual behaviour changes.
Inhaler technique: does age matter? A systematic review
Authors: Barbara Sarah , Kritikos Vicky , Bosnic-Anticevich Sinthia
Published: December 2017

Poor inhaler technique and inferior asthma outcomes are evident in older adults. Reviews comparing metered dose inhaler (MDI) and dry powder inhaler (DPI) techniques across older adults and younger cohorts are scarce. This systematic review aimed to determine whether differences exist between such cohorts with regards to the number and type of MDI and DPI errors made. A systematic literature search was conducted in Embase, Medline and PubMed from July 1 to December 31, 2016. Studies were selected in accordance with preset inclusion criteria, relevant data were extracted, and quality was assessed with validated checklists. 14 studies were identified. Evidence suggests a negative correlation between advancing age and correct technique across MDI and varying DPI devices when examined collectively. Differences appear to exist between older adult and younger cohorts prescribed MDIs in error types. There is evidence of age-associated differences in the number and type of inhaler technique errors. Further research is required to assess outcomes in individual DPIs, reproducibility and the effects of confounders.
Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis
Authors: Lancaster Lisa H. , de Andrade Joao A. , Zibrak Joseph D. , Padilla Maria L. , Albera Carlo , Nathan Steven D. , Wijsenbeek Marlies S. , Stauffer John L. , Kirchgaessler Klaus-Uwe , Costabel Ulrich
Published: December 2017

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequentpost hocanalyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs.
Lung ageing and COPD: is there a role for ageing in abnormal tissue repair?
Authors: Brandsma Corry-Anke , de Vries Maaike , Costa Rita , Woldhuis Roy R. , Königshoff Melanie , Timens Wim
Published: December 2017

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death worldwide, with increasing prevalence, in particular in the elderly. COPD is characterised by abnormal tissue repair resulting in (small) airways disease and emphysema. There is accumulating evidence that ageing hallmarks are prominent features of COPD. These ageing hallmarks have been described in different subsets of COPD patients, in different lung compartments and also in a variety of cell types, and thus might contribute to different COPD phenotypes. A better understanding of the main differences and similarities between normal lung ageing and the pathology of COPD may improve our understanding of the mechanisms driving COPD pathology, in particular in those patients that develop the most severe form of COPD at a relatively young age,i.e.severe early-onset COPD patients.

In this review, after introducing the main concepts of lung ageing and COPD pathology, we focus on the role of (abnormal) ageing in lung remodelling and repair in COPD. We discuss the current evidence for the involvement of ageing hallmarks in these pathological features of COPD. We also highlight potential novel treatment strategies and opportunities for future research based on our current knowledge of abnormal lung ageing in COPD.
Identifying a Clinically Applicable Mutational Burden Threshold as a Potential Biomarker of Response to Immune Checkpoint Therapy in Solid Tumors
Authors: Panda Anshuman , Betigeri Anil , Subramanian Kalyanasundaram , Ross Jeffrey S. , Pavlick Dean C. , Ali Siraj , Markowski Paul , Silk Ann , Kaufman Howard L. , Lattime Edmund , Mehnert Janice M. , Sullivan Ryan , Lovly Christine M. , Sosman Jeffrey , Johnson Douglas B. , Bhanot Gyan , Ganesan Shridar
Published: December 2017

Purpose

An association between mutational burden and response to immune checkpoint therapy has been documented in several cancer types. The potential for such a mutational burden threshold to predict response to immune checkpoint therapy was evaluated in several clinical datasets, where mutational burden was measured either by whole-exome sequencing or by using commercially available sequencing panels.

Methods

Whole-exome sequencing and RNA sequencing data of 33 solid cancer types from The Cancer Genome Atlas were analyzed to determine whether a robust immune checkpoint–activating mutation (iCAM) burden threshold associated with evidence of immune checkpoint activation exists in these cancers that may serve as a biomarker of response to immune checkpoint blockade therapy.

Results

We found that a robust iCAM threshold, associated with signatures of immune checkpoint activation, exists in eight of 33 solid cancers: melanoma, lung adenocarcinoma, colon adenocarcinoma, endometrial cancer, stomach adenocarcinoma, cervical cancer, estrogen receptor–positive/human epidermal growth factor receptor 2–negative breast cancer, and bladder-urothelial cancer. Tumors with a mutational burden higher than the threshold (iCAM positive) also had clear histologic evidence of lymphocytic infiltration. In published datasets of melanoma, lung adenocarcinoma, and colon cancer, patients with iCAM-positive tumors had significantly better response to immune checkpoint therapy compared with those with iCAM-negative tumors. Receiver operating characteristic analysis using The Cancer Genome Atlas predictions as the gold standard showed that iCAM-positive tumors are accurately identifiable using clinical sequencing assays, such as FoundationOne (Foundation Medicine, Cambridge, MA) or StrandAdvantage (Strand Life Sciences, Bangalore, India). Using the FoundationOne-derived threshold, an analysis of 113 melanoma tumors showed that patients with iCAM-positive disease have significantly better response to immune checkpoint therapy. iCAM-positive and iCAM-negative tumors have distinct mutation patterns and different immune microenvironments.

Conclusion

In eight solid cancers, a mutational burden threshold exists that may predict response to immune checkpoint blockade. This threshold is identifiable using available clinical sequencing assays.
Anti–PD-L1 Treatment Induced Central Diabetes Insipidus
Authors: Zhao Chen , Tella Sri Harsha , Del Rivero Jaydira , Kommalapati Anuhya , Ebenuwa Ifechukwude , Gulley James , Strauss Julius , Brownell Isaac
Published: December 2017

Context

Immune checkpoint inhibitors, including anti–programmed cell death protein 1 (PD-1), anti–programmed cell death protein ligand 1 (PD-L1), and anti–cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) monoclonal antibodies, have been widely used in cancer treatment. They are known to cause immune-related adverse events (irAEs), which resemble autoimmune diseases. Anterior pituitary hypophysitis with secondary hypopituitarism is a frequently reported irAE, especially in patients receiving anti–CTLA4 treatment. In contrast, posterior pituitary involvement, such as central diabetes insipidus (DI), is relatively rare and is unreported in patients undergoing PD-1/PD-L1 blockade.

Case Description

We describe a case of a 73-year-old man with Merkel cell carcinoma who received the anti–PD-L1 monoclonal antibody avelumab and achieved partial response. The patient developed nocturia, polydipsia, and polyuria 3 months after starting avelumab. Further laboratory testing revealed central DI. Avelumab was held and he received desmopressin for the management of central DI. Within 6 weeks after discontinuation of avelumab, the patient’s symptoms resolved and he was eventually taken off desmopressin. The patient remained off avelumab and there were no signs or symptoms of DI 2 months after the discontinuation of desmopressin.

Conclusion

To our knowledge, this is the first report of central DI associated with anti–PD-L1 immunotherapy. The patient’s endocrinopathy was successfully managed by holding treatment with the immune checkpoint inhibitor. This case highlights the importance of early screening and appropriate management of hormonal irAEs in subjects undergoing treatment with immune checkpoint inhibitors to minimize morbidity and mortality.
Protein synthesis is lowered by 4EBP1 and eIF2-α signaling while protein degradation may be maintained in fasting, hypoxic Amazonian cichlid, Astronotus ocellatus
Authors: Cassidy A. A. , Driedzic W. R. , Campos D. , Heinrichs-Caldas W. , Almeida-Val V. M. F. , Val A. L. , Lamarre S. G.
Published: December 2017

The Amazonian cichlid, Astronotus ocellatus, is highly tolerant to hypoxia, and is known to reduce its metabolic rate by reducing the activity of energetically expensive metabolic processes when oxygen is lacking in their environment. Our objectives were to determine how protein metabolism is regulated in A. ocellatus during hypoxia. Fish were exposed to a stepwise decrease in air saturation (100%, 20%, 10% and 5%) for 2 hours at each level, and sampled throughout the experiment. A flooding dose technique using a stable isotope allowed us to observe an overall decrease in protein synthesis during hypoxia in liver, muscle, gill and heart. We estimate that this decrease in rates of protein synthesis accounts for a 20 to 36% decrease in metabolic rate, which would enable oscars to maintain stable levels of ATP and prolong survival. It was also determined for the first time in fish that a decrease in protein synthesis during hypoxia is likely controlled by signaling molecules (4EBP1 and eIF2-α), and not simply due to a lack of ATP. We could not detect any effects of hypoxia on protein degradation as the levels of NH4 excretion, indicators of the ubiquitin proteasome pathway, and enzymatic activities of lysosomal and non-lysosomal proteolytic enzymes were maintained throughout the experiment.