bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyranoside‐into‐Furanoside Rearrangement of 4‐Pentenyl Glycosides in the Synthesis of a Tetrasaccharide‐Related to Galactan I of Klebsiella pneumoniae
Authors: Verkhnyatskaya Stella A. , Krylov Vadim B. , Nifantiev Nikolay E.
Published: December 2016

An efficient strategy for synthesis of a spacer‐armed tetrasaccharide related to galactan I of Klebsiella pneumoniae is described, which uses newly developed acid‐free conditions for the pyranoside‐into‐furanoside (PIF) rearrangement of a digalactoside bearing a 4‐pentenyl group at the anomeric position. The 4‐pentenyl aglycon was successfully used both as a leaving group in the glycosylation of 3‐(trifluoroacetamido)propanol, and as a temporary anomeric protecting group, allowing conversion into an imidate donor. Regioselective coupling of the disaccharide blocks gave the desired tetrasaccharide sequence required for investigation of the interaction of galactan I with immune‐system proteins.
Revisiting precipitation variability, trends and drivers in the Canary Islands
Authors: Sánchez‐Benítez Antonio , García‐Herrera Ricardo , Vicente‐Serrano Sergio M.
Published: December 2016

The Canary Islands are characterized by their low availability of water resources and different studies have suggested a decrease of precipitation in the second half of the 20th century. Here, we have used the most complete precipitation data set available in the islands to create a dense high quality and homogeneous database, which was used to determine the spatio‐temporal precipitation patterns in the archipelago and the influence of oceanic and atmospheric teleconnections. We have produced a robust regionalization of the Canary Islands precipitation, with three patterns that characterizing the south of the most montainous islands and El Hierro and La Gomera, the north of the most montainous islands and the easternmost arid islands (Lanzarote and Fuerteventura), respectively. All of them show high interannual variability, with no significant trends, except in a few cases. We highlight the strong influence of weather types and teleconections, modulated by the orography, with the highest influence recorded in the first pattern. It must be stressed that the oceanic teleconnections (in special with the tropical North Atlantic surface temperature) are more important than the North Atlantic Oscillation to explain interannual variability of precipitation.
Molecular doping of graphene across ultra‐thin molybdenum disulphide spacers
Authors: George Lijin , Shaina Punnakkaparambil R. , Afsal Kareekunnan , Jaiswal Manu
Published: December 2016

Molecular doping of graphene is intriguing since the electronic and vibrational properties of graphene are not only determined by the interfacial charge transfer process, but they can also be influenced by adsorbate–graphene hybridization, adsorbate–adsorbate interactions, as well as Fermi‐level pinning of the molecule. In this work, we investigate the change in vibrational properties of graphene induced by an organic electron acceptor molecule in the presence of intervening spacers of ultra‐thin molybdenum disulphide (MoS2) of variable thickness, down to a single layer. Mechanically exfoliated single‐layer graphene and few‐layer MoS2 crystals are combined to form heterostructures, which are then subjected to molecular doping by means of an organic hole‐dopant, 7,7,8,8‐tetracyanoquinodimethane (TCNQ). Variations in Raman G‐peak parameters are discussed in terms of molecular doping of graphen e, when the dopant:graphene separation is controllably increased. We show that dopant‐separation dependent Fermi level variations of graphene cannot be completely accounted within a simple charge transfer model. The additional mechanisms relevant to the complex nature of molecular doping are discussed.
The development of autism spectrum disorders: variability and causal complexity
Authors: Wozniak Robert H. , Leezenbaum Nina B. , Northrup Jessie B. , West Kelsey L. , Iverson Jana M.
Published: December 2016

The autism spectrum is highly variable, both behaviorally and neurodevelopmentally. Broadly speaking, four related factors contribute to this variability: (1) genetic processes, (2) environmental events, (3) gene × environment interactions, and (4) developmental factors. Given the complexity of the relevant processes, it appears unlikely that autism spectrum atypicalities can be attributed to any one causal mechanism. Rather, the development of neural atypicality reflects an interaction of genetic and environmental risk factors. As the individual grows, changes in neural atypicality, consequent variation in behavior, and environmental response to that behavior may become linked in a positive feedback loop that amplifies deviations from the typical developmental pattern.WIREs Cogn Sci2017, 8:e1426. doi: 10.1002/wcs.1426

This article is categorized under:

Neuroscience > Clinical Neuroscience

Neuroscience > Development
Risk of pathogen spillover to bighorn sheep from domestic sheep and goat flocks on private land
Authors: Heinse Laura M. , Hardesty Linda H. , Harris Richard B.
Published: December 2016

Bighorn sheep (Ovis canadensis) across North America have suffered population losses due to polymicrobial pneumonia typically initiated by spillover events of bacteria from domestic sheep and goats. Because vaccination or treatment of individual animals remains an elusive goal and pneumonia often persists in bighorn herds for years or decades following infection, preventing contact between domestic and wild animals is widely accepted as the best prophylactic. For the past decade, most management efforts have focused on the risks associated with commercial sheep grazing on public lands; less attention has been paid to risks to bighorns from small flocks of domestic sheep and goats managed entirely on private land. We surveyed owners of 40 sheep or goat flocks located near bighorn sheep herds in central and southeastern Washington, USA, during 2014 and 2015, to better understand their knowledge level, management practices, and willingness to reduce risks. Over one‐third of sheep or goat owners had no knowledge of the potential for pathogen spillover to bighorns, but all were interested in reducing risk of interacting with bighorns, particularly by options that did not restrict their autonomy. We also sampled nasal mucosae of 137 animals in 24 flocks for presence of Mycoplasma ovipneumoniae, the bacterium most closely associated with bighorn pneumonia. M. ovipneumoniae was detected in 37.5% of sheep or goat flocks sampled, and animals had escaped their enclosures in 78% of these. Physical contact, and thus pathogen spillover from domestic sheep or goats living in small, private flocks in close proximity to bighorns is clearly a risk. We provide recommendations to agency staff on identifying, prioritizing and testing small herds, and then working with owners to reduce the risk of pathogen spillover. © 2016 The Wildlife Society.
Subacromial spacer implantation for massive rotator cuff tears
Authors: Holschen Malte , Brand Florian , Agneskirchner Jens D.
Published: December 2016

Background

Massive rotator cuff tears (MRCT) can be treated arthroscopically by partial reconstruction, tenotomy/tenodesis of the long head of the biceps, and debridement. A new treatment option is the additional implantation of a biodegradable spacer (InSpace Balloon®; ISB) into the subacromial space, which reduces subacromial shear forces to keep the humeral head centered in the glenoid. The aim of this study is to investigate the clinical outcome of patients with MRCT who were treated arthroscopically with or without an additional ISB.

Methods

The clinical outcome of patients treated with conventional arthroscopic techniques (n = 11, group A, partial repair, biceps tenotomy, and debridement) and that of patients treated with a supplementary ISB (n = 12, group B) was retrospectively analyzed. Preoperatively and postoperatively, shoulder function was assessed with the Constant and American Shoulder and Elbow Surgeons (ASES) scores. At follow-up after a mean of 22 months, patients filled out a questionnaire about their subjective satisfaction.

Results

Preoperative shoulder function was lower in patients treated with an ISB (ASES score: group A, 59.1; group B, 31.5; Constant score: group A, 60.7; group B, 36.8). At follow-up, both groups had improved shoulder function (Constant score: group A, 60.7–77.6; p < 0.001; group B, 36.8–69.5; p < 0.001; ASES score: group A, 59.1–88.6; p < 0.001; group B, 31.5–85.7; p < 0.001). Patients in both groups were subjectively satisfied with their outcome.

Conclusion

The ISB is a feasible treatment option for MRCT, providing subjective pain relief and improved shoulder function. Further studies with larger patient collectives and longer follow-up are needed to confirm whether it is a safe and cost-effective treatment.
Subsyndromal delirium compared with delirium, dementia, and subjects without delirium or dementia in elderly general hospital admissions and nursing home residents
Authors: Sepulveda Esteban , Leonard Maeve , Franco Jose G. , Adamis Dimitrios , McCarthy Geraldine , Dunne Colum , Trzepacz Paula T. , Gaviria Ana M. , de Pablo Joan , Vilella Elisabet , Meagher David J.
Published: December 2016

Introduction

Subsyndromal delirium (SSD) complicates diagnosis of delirium and dementia, although there is little research comparing their symptom profiles.

Methods

Cross‐sectional study of 400 elderly patients' admission to a general hospital or nursing home diagnosed with delirium, SSD, dementia, or no‐delirium/no‐dementia (NDND). Symptom profiles were assessed using the Delirium Rating Scale‐Revised‐98 (DRS‐R98).

Results

Twenty percent patients had delirium, 19.3% had SSD, 29.8% had dementia‐only, and 31% had NDND. Eighty‐one percent of subsyndromal and 76% of delirium groups had comorbid dementia. DRS‐R98 scores showed ascending severity from NDND < dementia‐only < SSD < delirium. DRS‐R98 scores for items evaluating the three core symptom domains (cognitive, higher‐order thinking, and circadian) distinguished SSD from delirium and both from nondelirium groups. DRS‐R98 profiles were essentially the same in delirium and SSD subgroups with or without dementia, although total scale scores were generally higher when in comorbid subgroups.

Discussion

SSD shared characteristic core domain symptoms with delirium, which distinguished each from nondelirium groups, although severity was intermediate in the subsyndromal group. Delirium core symptoms overshadowed the dementia phenotype when comorbid. Milder disturbances of delirium core domain symptoms are highly suggestive of SSD.
Isolated cochlear neuritis from varicella reactivation mimicking a vestibular schwannoma
Authors: Goodale Adam D. , Golub Justin S. , Cornelius Rebecca S. , Samy Ravi N.
Published: December 2016

We present a case of a patient with progressive unilateral sensorineural hearing loss and tinnitus with internal auditory canal enhancement on magnetic resonance imaging (MRI) secondary to isolated cochlear neuritis from varicella reactivation. MRI following antiviral treatment showed resolution of enhancement. Varicella reactivation is commonly seen in the form of Ramsay Hunt syndrome, which is known to produce abnormal MRI enhancement from facial and vestibulocochlear neuritis; however, its characteristic clinical signs aid the diagnosis. This case is unique in that the only manifestation of varicella infection was unilateral hearing loss. This case outlines the importance of maintaining a broad differential diagnosis in the evaluation of unilateral hearing loss as well as recognizing the limited specificity of MRI.
An investigation of empirical formulation and design optimisation of co-flow fluidic thrust vectoring nozzles
Authors: Banazadeh A. , Saghafi F.
Published: December 2016

The purpose of this paper is to design and develop an advanced co-flow fluidic nozzle, based on the Coanda effect concept, for multi-directional thrust vectoring of small jet engines. Recent progress on finding an optimal geometry with a fixed momentum ratio to achieve maximum thrust deflection angle is discussed here. The efficiency of the system is found to be a weakly nonlinear function of the secondary to primary flow momentum as well as three geometric parameters. A useful empirical formulation is derived for thrust vectoring angle, based on a series of tests carried out on different nozzles. An accurate computational fluid dynamics model is also developed and evaluated against the experimental data. Moreover, quasi-Newton optimisation algorithm is employed to find an optimal geometry with a constant relative jet momentum and a constant secondary slot size. In this technique, the optimal wall geometric parameters are calculated in the direction of the steepest gradient with the help of the numerical simulation model in every iteration step. Additionally, an optimised fluidic nozzle is constructed to experimentally verify the numerical results and the empirical equation.
Social Disinhibition: Piloting a New Clinical Measure in Individuals with Traumatic Brain Injury
Authors: Honan Cynthia A. , Allen Samantha K. , Fisher Alana , Osborne-Crowley Katherine , McDonald Skye
Published: December 2016

Social disinhibition difficulties are common following traumatic brain injury (TBI). However, clinically sensitive tools to objectively assess the difficulties are lacking. This study aimed to pilot a new clinical measure of social disinhibition, the social disinhibition task (SDT). Whether social disinhibition is dependent on the type of social information judgements required and whether disinhibited responses can be adjusted with additional guidance were also examined. Participants were 31 adults (25 Male) with moderate-to-severe TBI and 22 adult (17 Male) healthy control participants. Participants viewed scenes of complex social situations and were asked to describe a character in them (Part A), describe a character while inhibiting inappropriate or negative responses (Part B), and describe a character while not only inhibiting negative responses, but also providing positive responses (Part C). One-half of the items contained a faux pas requiring participants to make inferences about a character's mental state. TBI and control participants responded similarly to Part A, although control participants responded less positively than TBI participants in the faux pas items. TBI participants were significantly impaired on Part B indicating they experienced difficulties in inhibiting automatic responding. TBI participants were however able to adjust their responding in Part C so that they respond similarly to the control participants. Between group differences were not detected in reaction time. Overall, the SDT appears to be suitable to detect social inhibition difficulties in clinical settings and provides a new direction for remediation of the difficulties in individuals with TBI.
SEPARATING FRAGMENTS OF WLEM, LPO, AND MP
Authors: HENDTLASS MATT , LUBARSKY ROBERT
Published: December 2016

We separate many of the basic fragments of classical logic which are used in reverse constructive mathematics. A group of related Kripke and topological models is used to show that various fragments of the Weak Law of the Excluded Middle, the Limited Principle of Omniscience, and Markov’s Principle, including Weak Markov’s Principle, do not imply each other.
MODIFIED EXTENDER BASED FORCING
Authors: SINAPOVA DIMA , UNGER SPENCER
Published: December 2016

We analyze the modified extender based forcing from Assaf Sharon’s PhD thesis. We show there is a bad scale in the extension and therefore weak square fails. We also present two metatheorems which give a rough characterization of when a diagonal Prikry-type forcing forces the failure of weak square.
SPECTRAL ZETA FUNCTIONS FOR THE QUANTUM RABI MODELS
Authors: SUGIYAMA SHINGO
Published: December 2016

We introduce the Hurwitz-type spectral zeta functions for the quantum Rabi models, and give their meromorphic continuation to the whole complex plane with only one simple pole at$s=1$. As an application, we give the Weyl law for the quantum Rabi models. As a byproduct, we also give a rationality of Rabi–Bernoulli polynomials introduced in this paper.
Late Permian to Triassic isotope composition of sulfates in the Eastern Alps: palaeogeographic implications
Authors: BOJAR ANA-VOICA , HAŁAS STANISLAW , BOJAR HANS-PETER , TREMBACZOWSKI ANDRZEJ
Published: December 2016

Late Permian to Triassic phases from the evaporite deposits of the Northern Calcareous Alps (NCA) and Central Alpine Mesozoic (CAM) were analysed for sulfur and oxygen isotope compositions. For the Upper Permian, most of the δ34S values are in the 11 to 12‰ range. Röt-type sulfates of Early Triassic age are characterized by a heavy sulfur isotopic composition of c. 26‰. The spatial compilation of the available data concerning the isotopic composition of Röt-type sulfates demonstrates that these evaporites are distributed over the entire area of the NCA. Their occurrences are associated with Early Triassic high-temperature conditions of the seawater and a widespread anoxia. The development of sulfates of Carnian–Norian age situated in the CAM is more modest; sulfates are characterized by a δ34S value of c. 15‰. The δ18O values show a broader distribution from 9 to 22‰, related to several factors such as type of deposit, recrystallization processes and bacterial sulfate reduction. The sulfate–sulfide thermometer applied to samples from NCA deposits indicates a thermal overprint of between 215 and 315°C. Microbeam measurements support zonation of minor elements in sphalerite. Sphalerite microstructure indicates thermal overprinting, with no microbial structure being preserved.
Does Foreign Aid Target the Poorest?
Authors: Briggs Ryan C.
Published: December 2016

To examine the extent to which foreign aid reaches people at different levels of wealth in Africa, I use household surveys to measure the subnational distribution of a country's population by wealth quintiles and match this information to data on the location of aid projects from two multilateral donors. Within countries, aid disproportionately flows to regions with more of the richest people. Aid does not favor regions with more of the poorest people. These findings violate the stated preferences of the multilateral donors under study, suggesting that the donors either cannot or are not willing to exercise control over the location of aid projects within countries. The results also suggest that aid is not being allocated effectively to alleviate extreme poverty.
Grammar of Difference? The Dutch Colonial State, Labour Policies, and Social Norms on Work and Gender, c.1800–1940
Authors: van Nederveen Meerkerk Elise
Published: December 2016

This article investigates developments in labour policies and social norms on gender and work from a colonial perspective. It aims to analyse the extent to which state policies and societal norms influenced gendered labour relations in the Netherlands and its colony, the Netherlands Indies (present-day Indonesia). In order to investigate the influence of the state on gender and household labour relations in the Dutch empire, this paper compares as well as connects social interventions related to work and welfare in the Netherlands and the Netherlands Indies from the early nineteenth century up until World War II. At the beginning of the nineteenth century, work was seen as a means to morally discipline the poor, both in the Netherlands and the Netherlands Indies. Parallel initiatives were taken by Johannes van den Bosch, who, in 1815, established “peat colonies” in the Netherlands, aiming to transform the urban poor into industrious agrarian workers, and in 1830 introduced the Cultivation System in the Netherlands Indies, likewise to increase the industriousness of Javanese peasants. While norms were similar, the scope of changing labour relations was much vaster in the colony than in the metropole.

During the nineteenth century, ideals and practices of the male breadwinner started to pervade Dutch households, and children’s and women’s labour laws were enacted. Although in practice many Dutch working-class women and children continued to work, their official numbers dropped significantly. In contrast to the metropole, the official number of working (married) women in the colony was very high, and rising over the period. Protection for women and children was introduced very late in the Netherlands Indies and only under intense pressure from the international community. Not only did Dutch politicians consider it “natural” for Indonesian women and children to work, their assumptions regarding inherent differences between Indonesian and Dutch women served to justify the protection of the latter: a fine example of what Ann Stoler and Frederick Cooper have called a “grammar of difference”.
Conquerors, Employers, and Arbiters: States and Shifts in Labour Relations 1500–2000, Introduction
Authors: Hofmeester Karin , Kessler Gijs , Moll-Murata Christine
Published: December 2016

The introductory article to this volume offers an analytical framework for the capacities in which states have historically affected labour relations. The framework captures the full range of possible manifestations of state power, including early states, empires, regional authorities, and city states. It distinguishes between the state as a direct actor or participant, carrying out tasks deemed essential for its functioning, and the state as an arbiter, redistributor, or regulator. As conquerors or employers, states are confronted with a basic dilemma: how to extract and allocate the labour resources required to accomplish state tasks. Borrowing from Charles Tilly, the two broad categories of capital and coercion are used as a heuristic device to bring order to the ways in which states have solved this dilemma. Contrary to Tilly’s trajectories of state formation, states’ reliance on capital or coercion is subject to a great degree of flexibility, both over time and across space. In their capacities as mediators and regulators, modern states came to have an even more profound impact on labour relations, as state building moved away from the single focus on organizing the extraction of resources to a wider mission of fostering welfare, economic development, and human capital formation.
In vitro bioavailability and cellular bioactivity studies of flavonoids and flavonoid-rich plant extracts: questions, considerations and future perspectives
Authors: Gonzales Gerard Bryan
Published: December 2016

In vitro techniques are essential in elucidating biochemical mechanisms and for screening a wide range of possible bioactive candidates. The number of papers published reporting in vitro bioavailability and bioactivity of flavonoids and flavonoid-rich plant extracts is numerous and still increasing. However, even with the present knowledge on the bioavailability and metabolism of flavonoids after oral ingestion, certain inaccuracies still persist in the literature, such as the use of plant extracts to study bioactivity towards vascular cells. There is therefore a need to revisit, even question, these approaches in terms of their biological relevance. In this review, the bioavailability of flavonoid glycosides, the use of cell models for intestinal absorption and the use of flavonoid aglycones and flavonoid-rich plant extracts in in vitro bioactivity studies will be discussed. Here, we focus on the limitations of current in vitro systems and revisit the validity of some in vitro approaches, and not on the detailed mechanism of flavonoid absorption and bioactivity. Based on the results in the review, there is an apparent need for stricter guidelines on publishing data on in vitro data relating to the bioavailability and bioactivity of flavonoids and flavonoid-rich plant extracts.
Prescriptive infinitives in the modern North Germanic languages: An ancient phenomenon in child-directed speech
Authors: Johannessen Janne Bondi
Published: December 2016

The prescriptive infinitive can be found in the North Germanic languages, is very old, and yet is largely unnoticed and undescribed. It is used in a very limited pragmatic context of a pleasant atmosphere by adults towards very young children, or towards pets or (more rarely) adults. It has a set of syntactic properties that distinguishes it from the imperative: Negation is pre-verbal, subjects are pre-verbal, subjects are third person and are only expressed by lexical DPs, not personal pronouns. It can be found in modern child language corpora, but probably originated beforead500. The paper is largely descriptive, but some theoretical solutions to the puzzles of this construction are proposed.
The rise and fall of hospitalizations for skin infections in New Zealand, 2004–2014: trends by ethnicity and socioeconomic deprivation
Authors: LIM A. , RUMBALL-SMITH J. , JONES R. , KAWACHI I.
Published: December 2016

Since the 1990s, New Zealand (NZ) has seen an increasing incidence of paediatric skin infections leading to hospitalization. We sought to describe the epidemiology of these infections over time. Hospital discharge data were analysed for all children admitted to any NZ public hospital from 2004 to 2014. We found the age-standardized incidence of hospitalizations due to skin infections increased during this period from 522/100 000 in 2004 to a peak of 644/100 000 in 2011, after which it declined to 524/100 000 in 2014. This decline in incidence was driven primarily by the decline in hospitalization rates in high-risk groups including children living in the most deprived areas as well as Māori and Pacific children. Recent targeted policies focused on improving healthcare access through school-based and primary care-based interventions in these high-risk groups could potentially explain the decline in hospitalization rates. However, even with the closing of the inequality gap, significant socioeconomic and ethnic health disparities persist.
Epidemiological and serological investigation of a waterborneCampylobacter jejunioutbreak in a Danish town
Authors: KUHN K. GAARDBO , FALKENHORST G. , EMBORG H.-D. , CEPER T. , TORPDAHL M. , KROGFELT K. A. , ETHELBERG S. , MØLBAK K.
Published: December 2016

Following an unusually heavy rainfall in June 2009, a community-wide outbreak ofCampylobactergastroenteritis occurred in a small Danish town. The outbreak investigation consisted of (1) a cohort study using an e-questionnaire of disease determinants, (2) microbiological study of stool samples, (3) serological study of blood samples from cases and asymptomatic members of case households, and (4) environmental analyses of the water distribution system. The questionnaire study identified 163 cases (respondent attack rate 16%). Results showed a significant dose-response relationship between consumption of tap water and risk of gastroenteritis.Campylobacter jejunibelonging to two relatedflaAtypes were isolated from stool samples. Serum antibody levels againstCampylobacterwere significantly higher in cases than in asymptomatic persons. Water samples were positive for coliform bacteria, and the likely mode of contamination was found to be surface water leaking into the drinking-water system. This geographically constrained outbreak presented an ideal opportunity to study the serological response in persons involved in aCampylobacteroutbreak. The serology indicated that asymptomatic persons from the same household may have been exposed, during the outbreak period, toCampylobacterat doses that did not elicit symptoms or alternatively had been exposed toCampylobacterat a time prior to the outbreak, resulting in residual immunity and thus absence of clinical signs.
Distribution and origin of ground ice in University Valley, McMurdo Dry Valleys, Antarctica
Authors: Lapalme Caitlin , Lacelle Denis , Pollard Wayne , Fisher David , Davila Alfonso , Mckay Christopher P.
Published: December 2016

Ground ice is one of the most important and dynamic geologic components of permafrost; however, few studies have investigated the distribution and origin of ground ice in the McMurdo Dry Valleys of Antarctica. In this study, ice-bearing permafrost cores were collected from 18 sites in University Valley, a small hanging glacial valley in the Quartermain Mountains. Ground ice was found to be ubiquitous in the upper 2 m of permafrost soils, with excess ice contents reaching 93%, but ground ice conditions were not homogeneous. Ground ice content was variable within polygons and along the valley floor, decreasing in the centres of polygons and increasing in the shoulders of polygons towards the mouth of the valley. Ground ice also had different origins: vapour deposition, freezing of partially evaporated snow meltwater and buried glacier ice. The variability in the distribution and origin of ground ice can be attributed to ground surface temperature and moisture conditions, which separate the valley into distinct zones. Ground ice of vapour-deposition origin was predominantly situated in perennially cryotic zones, whereas ground ice formed by the freezing of evaporated snow meltwater was predominantly found in seasonally non-cryotic zones.
Biomarkers in Prodromal Parkinson Disease: a Qualitative Review
Authors: Cooper Christine A. , Chahine Lama M.
Published: December 2016

Background: Over the past several years, the concept of prodromal Parkinson disease (PD) has been increasingly recognized. This term refers to individuals who do not fulfill motor diagnostic criteria for PD, but who have clinical, genetic, or biomarker characteristics suggesting risk of developing PD in the future. Clinical diagnosis of prodromal PD has low specificity, prompting the need for objective biomarkers with higher specificity. In this qualitative review, we discuss objectively defined putative biomarkers for PD and prodromal PD. Methods: We searched Pubmed and Embase for articles pertaining to objective biomarkers for PD and their application in prodromal cohorts. Articles were selected based on relevance and methodology. Key Findings: Objective biomarkers of demonstrated utility in prodromal PD include ligand-based imaging and transcranial sonography. Development of serum, cerebrospinal fluid, and tissue-based biomarkers is underway, but their application in prodromal PD has yet to meaningfully occur. Combining objective biomarkers with clinical or genetic prodromal features increases the sensitivity and specificity for identifying prodromal PD. Conclusions: Several objective biomarkers for prodromal PD show promise but require further study, including their application to and validation in prodromal cohorts followed longitudinally. Accurate identification of prodromal PD will likely require a multimodal approach. (JINS, 2016, 22, 956–967)
Patterns of Cortical and Subcortical Amyloid Burden across Stages of Preclinical Alzheimer’s Disease
Authors: Edmonds Emily C. , Bangen Katherine J. , Delano-Wood Lisa , Nation Daniel A. , Furst Ansgar J. , Salmon David P. , Bondi Mark W. ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2016

Objectives: We examined florbetapir positron emission tomography (PET) amyloid scans across stages of preclinical Alzheimer’s disease (AD) in cortical, allocortical, and subcortical regions. Stages were characterized using empirically defined methods. Methods: A total of 312 cognitively normal Alzheimer’s Disease Neuroimaging Initiative participants completed a neuropsychological assessment and florbetapir PET scan. Participants were classified into stages of preclinical AD using (1) a novel approach based on the number of abnormal biomarkers/cognitive markers each individual possessed, and (2) National Institute on Aging and the Alzheimer’s Association (NIA-AA) criteria. Preclinical AD groups were compared to one another and to a mild cognitive impairment (MCI) sample on florbetapir standardized uptake value ratios (SUVRs) in cortical and allocortical/subcortical regions of interest (ROIs). Results: Amyloid deposition increased across stages of preclinical AD in all cortical ROIs, with SUVRs in the later stages reaching levels seen in MCI. Several subcortical areas showed a pattern of results similar to the cortical regions; however, SUVRs in the hippocampus, pallidum, and thalamus largely did not differ across stages of preclinical AD. Conclusions: Substantial amyloid accumulation in cortical areas has already occurred before one meets criteria for a clinical diagnosis. Potential explanations for the unexpected pattern of results in some allocortical/subcortical ROIs include lack of correspondence between (1) cerebrospinal fluid and florbetapir PET measures of amyloid, or between (2) subcortical florbetapir PET SUVRs and underlying neuropathology. Findings support the utility of our novel method for staging preclinical AD. By combining imaging biomarkers with detailed cognitive assessment to better characterize preclinical AD, we can advance our understanding of who is at risk for future progression. (JINS, 2016, 22, 978–990)
The theory of capital as a theory of capitalism
Authors: BRAUN EDUARD
Published: December 2016

Before economists and sociologists came up with their own definitions of the term ‘capital’, it was commonly understood as money invested in businesses by their owners or shareholders, and it continues to be understood this way in everyday business practice. In a recent article, Hodgson (2014) advises economists to return to this pre-Smithian usage of the term. This paper takes up Hodgson's demand and develops a theory of capital that is based upon this business notion of capital. It also argues that the Austrian theory of capital, if interpreted correctly, can serve as a starting point. Despite the conviction of its adherents to the contrary, the Austrian theory of capital is not universal or ahistorical, but dovetails with Hodgson's vision of an approach to capital that analyses historically specific features of capitalism.
Introduction to the Douglass C. North memorial issue
Authors: HODGSON GEOFFREY M.
Published: December 2016

This introduction considers the highly influential contribution of Douglass C. North to economic history and institutional economics, as it developed from the 1960s until his death in 2015. It sketches the evolution of his arguments concerning the roles of institutions, organizations and human agency. North's conception of the economic actor became progressively more sophisticated, by acknowledging the role of ideology and adopting insights from cognitive science. Eventually, he abandoned the proposition that institutions are generally efficient, to propose instead that sub-optimal institutional forms could persist. A few noted criticisms of North's work are also considered here, ranging from those which are arguably off the mark, to others that retain some force. The contributions to this memorial issue are outlined at the end of this introduction.
A mechanism for overcoming P-glycoprotein-mediated drug resistance: novel combination therapy that releases stored doxorubicin from lysosomes via lysosomal permeabilization using Dp44mT or DpC
Authors: Seebacher Nicole A , Richardson Des R , Jansson Patric J
Published: December 2016

The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers. Thus, the combination of these agents should be considered as an effective rationalized therapy for potently treating advanced and resistant tumors that are often heterogeneous in terms of Pgp-expression. These studies demonstrate that both Dp44mT and DpC are transported into lysosomes via Pgp transport activity, where they induce lysosomal-membrane permeabilization to release DOX trapped within lysosomes. This novel strategy of loading lysosomes with DOX, followed by permeabilization with Dp44mT or DpC, results in the relocalization of stored DOX from its lysosomal 'safe house' to its nuclear targets, markedly enhancing cellular toxicity against resistant tumor cells. Notably, the combination of Dp44mT or DpC with DOX showed a very high level of synergism in multiple Pgp-expressing cell types, for example, cervical, breast and colorectal cancer cells. These studies revealed that the level of drug synergy was proportional to Pgp activity. Interestingly, synergism was ablated by inhibiting Pgp using the pharmacological inhibitor, Elacridar, or by inhibiting Pgp-expression using Pgp-silencing, demonstrating the importance of Pgp in the synergistic interaction. Furthermore, lysosomal-membrane stabilization inhibited the relocalization of DOX from lysosomes to the nucleus upon combination with Dp44mT or DpC, preventing synergism. This latter observation demonstrated the importance of lysosomal-membrane permeabilization to the synergistic interaction between these agents. The synergistic and potent anti-tumor efficacy observed between DOX and thiosemicarbazones represents a promising treatment combination for advanced cancers, which are heterogeneous and composed of non-Pgp- and Pgp-expressing tumor cells.
‘Normalizing’ the malignant phenotype of luminal breast cancer cells via alpha(v)beta(3)-integrin
Authors: Abu-Tayeh Hanan , Weidenfeld Keren , Zhilin-Roth Alisa , Schif-Zuck Sagi , Thaler Sonja , Cotarelo Cristina , Tan Tuan Z , Thiery Jean P , Green Jeffrey E , Klorin Geula , Sabo Edmond , Sleeman Jonathan P , Tzukerman Maty , Barkan Dalit
Published: December 2016

Reestablishing tissue organization of breast cancer cells into acini was previously shown to override their malignant phenotype. In our study, we demonstrate that alpha(v)beta(3) integrin (Int-αvβ3), previously shown to play a role in cancer progression, promoted differentiation and growth arrest of organoids derived from luminal A breast cancer cells grown in their relevant three-dimensional microenvironment. These organoids differentiated into normal-like acini resembling a benign stage of breast tissue. Likewise, we demonstrate that Int-αvβ3 is selectively expressed in the epithelium of the benign stage of breast tissues, and is lost during the early stages of luminal A breast cancer progression. Notably, the organoids’ reversion into normal-like acini was mediated by cancer luminal progenitor-like cells expressing both EpCAMhighCD49flowCD24+ and Int-αvβ3. Furthermore, downregulation of Notch4 expression and downstream signaling was shown to mediate Int-αvβ3-induced reversion. Intriguingly, when luminal A breast cancer cells expressing Int-αvβ3 were injected into a humanized mouse model, differentiated tumors developed when compared with that generated by control cells. Hence, our data suggest that promoting differentiation of luminal A breast cancer cells by signaling emanating from Int-αvβ3 can potentially promote ‘normalization’ of their malignant phenotype and may prevent the malignant cells from progressing.
Distinct outcomes of CRL–Nedd8 pathway inhibition reveal cancer cell plasticity
Authors: Rulina Anastasia V , Mittler Frédérique , Obeid Patricia , Gerbaud Sophie , Guyon Laurent , Sulpice Eric , Kermarrec Frédérique , Assard Nicole , Dolega Monika E , Gidrol Xavier , Balakirev Maxim Y
Published: December 2016

Inhibition of protein degradation by blocking Cullin-RING E3 ligases (CRLs) is a new approach in cancer therapy though of unknown risk because CRL inhibition may stabilize both oncoproteins and tumor suppressors. Probing CRLs in prostate cancer cells revealed a remarkable plasticity of cells with TMPRSS2-ERG translocation. CRL suppression by chemical inhibition or knockdown of RING component RBX1 led to reversible G0/G1 cell cycle arrest that prevented cell apoptosis. Conversely, complete blocking of CRLs at a higher inhibitor dose-induced cytotoxicity that was amplified by knockdown of CRL regulator Cand1. We analyzed cell signaling to understand how varying degrees of CRL inhibition translated to distinct cell fates. Both tumor suppressor and oncogenic cell signaling pathways and transcriptional activities were affected, with pro-metastatic Wnt/β-catenin as the most upregulated. Suppression of the NF-κB pathway contributed to anti-apoptotic effect, and androgen receptor (AR) and ERG played decisive, though opposite, roles: AR was involved in protective quiescence, whereas ERG promoted apoptosis. These data define AR–ERG interaction as a key plasticity and survival determinant in prostate cancer and suggest supplementary treatments that may overcome drug resistance mechanisms regulated by AR–ERG interaction.
Impaired haematopoietic stem cell differentiation and enhanced skewing towards myeloid progenitors in aged caspase-2-deficient mice
Authors: Dawar Swati , Shahrin Nur Hezrin , Sladojevic Nikolina , D'Andrea Richard J , Dorstyn Loretta , Hiwase Devendra K , Kumar Sharad
Published: December 2016

The apoptotic cysteine protease caspase-2 has been shown to suppress tumourigenesis in mice and its reduced expression correlates with poor prognosis in some human malignancies. Caspase-2-deficient mice develop normally but show ageing-related traits and, when challenged by oncogenic stimuli or certain stress, show enhanced tumour development, often accompanied by extensive aneuploidy. As stem cells are susceptible to acquiring age-related functional defects because of their self-renewal and proliferative capacity, we examined whether loss of caspase-2 promotes such defects with age. Using young and aged Casp2−/− mice, we demonstrate that deficiency of caspase-2 results in enhanced aneuploidy and DNA damage in bone marrow (BM) cells with ageing. Furthermore, we demonstrate for the first time that caspase-2 loss results in significant increase in immunophenotypically defined short-term haematopoietic stem cells (HSCs) and multipotent progenitors fractions in BM with a skewed differentiation towards myeloid progenitors with ageing. Caspase-2 deficiency leads to enhanced granulocyte macrophage and erythroid progenitors in aged mice. Colony-forming assays and long-term culture-initiating assay further recapitulated these results. Our results provide the first evidence of caspase-2 in regulating HSC and progenitor differentiation, as well as aneuploidy, in vivo.
Structure of the RBM7–ZCCHC8 core of the NEXT complex reveals connections to splicing factors
Authors: Falk Sebastian , Finogenova Ksenia , Melko Mireille , Benda Christian , Lykke-Andersen Søren , Jensen Torben Heick , Conti Elena
Published: December 2016

The eukaryotic RNA exosome participates extensively in RNA processing and degradation. In human cells, three accessory factors (RBM7, ZCCHC8 and hMTR4) interact to form the nuclear exosome targeting (NEXT) complex, which directs a subset of non-coding RNAs for exosomal degradation. Here we elucidate how RBM7 is incorporated in the NEXT complex. We identify a proline-rich segment of ZCCHC8 as the interaction site for the RNA-recognition motif (RRM) of RBM7 and present the crystal structure of the corresponding complex at 2.0 Å resolution. On the basis of the structure, we identify a proline-rich segment within the splicing factor SAP145 with strong similarity to ZCCHC8. We show that this segment of SAP145 not only binds the RRM region of another splicing factor SAP49 but also the RRM of RBM7. These dual interactions of RBM7 with the exosome and the spliceosome suggest a model whereby NEXT might recruit the exosome to degrade intronic RNAs.
11.4% Efficiency non-fullerene polymer solar cells with trialkylsilyl substituted 2D-conjugated polymer as donor
Authors: Bin Haijun , Gao Liang , Zhang Zhi-Guo , Yang Yankang , Zhang Yindong , Zhang Chunfeng , Chen Shanshan , Xue Lingwei , Yang Changduk , Xiao Min , Li Yongfang
Published: December 2016

Simutaneously high open circuit voltage and high short circuit current density is a big challenge for achieving high efficiency polymer solar cells due to the excitonic nature of organic semdonductors. Herein, we developed a trialkylsilyl substituted 2D-conjugated polymer with the highest occupied molecular orbital level down-shifted by Si–C bond interaction. The polymer solar cells obtained by pairing this polymer with a non-fullerene acceptor demonstrated a high power conversion efficiency of 11.41% with both high open circuit voltage of 0.94 V and high short circuit current density of 17.32 mA cm−2 benefitted from the complementary absorption of the donor and acceptor, and the high hole transfer efficiency from acceptor to donor although the highest occupied molecular orbital level difference between the donor and acceptor is only 0.11 eV. The results indicate that the alkylsilyl substitution is an effective way in designing high performance conjugated polymer photovoltaic materials.
Singing for Lung Health—a systematic review of the literature and consensus statement
Authors: Lewis Adam , Cave Phoene , Stern Myra , Welch Lindsay , Taylor Karen , Russell Juliet , Doyle Anne-Marie , Russell Anne-Marie , McKee Heather , Clift Stephen , Bott Julia , Hopkinson Nicholas S
Published: December 2016

There is growing interest in Singing for Lung Health (SLH), an approach where patients with respiratory disease take part in singing groups, intended to improve their condition. A consensus group was convened in early 2016 to address issues including: the specific features that make SLH distinct from other forms of participation in singing; the existing evidence base via a systematic review; gaps in the evidence base including the need to define value-based outcome measures for sustainable commissioning of SLH; defining the measures needed to evaluate both individuals' responses to SLH and the quality of singing programmes. and core training, expertise and competencies required by singing group leaders to deliver high-quality programmes. A systematic review to establish the extent of the evidence base for SLH was undertaken. Electronic databases, including Pubmed, OVID Medline and Embase, Web of Science, Cochrane central register of controlled trials and PEDro, were used. Six studies were included in the final review. Quantitative data suggest that singing has the potential to improve health-related quality of life, particularly related to physical health, and levels of anxiety without causing significant side effects. There is a significant risk of bias in many of the existing studies with small numbers of subjects overall. Little comparison can be made between studies owing to their heterogeneity in design. Qualitative data indicate that singing is an enjoyable experience for patients, who consistently report that it helps them to cope with their condition better. Larger and longer-term trials are needed.
Validation of the breathlessness, cough and sputum scale to predict COPD exacerbation
Authors: DeVries Rebecca , Kriebel David , Sama Susan
Published: December 2016

The breathlessness, cough and sputum scale (BCSS) is a three-item questionnaire rating breathlessness, cough and sputum on a 5-point Likert scale from 0 (no symptoms) to 4 (severe symptoms). Researchers have explored the utility of this tool to quantify efficacy of treatment following a chronic obstructive pulmonary disease (COPD) exacerbation; however, little work has been done to investigate the ability of the BCSS to predict COPD exacerbation. As part of a prospective case-crossover study among a cohort of 168 COPD patients residing in central Massachusetts, patients were asked standard BCSS questions during exacerbation and randomly identified non-exacerbation (or healthy) weeks. We found that the BCSS was strongly associated with COPD exacerbation (OR=2.80, 95% CI=2.27–3.45) and that a BCSS sum score of 5.0 identified COPD exacerbation with 83% sensitivity and 68% specificity. These results may be useful in the clinical setting to expedite interventions of exacerbation.