bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic IgE Antibodies: Harnessing a Macrophage-Mediated Immune Surveillance Mechanism against Cancer
Authors: Karagiannis Sophia N. , Josephs Debra H. , Bax Heather J. , Spicer James F.
Published: May 2017

IgG monoclonal antibodies have made significant contributions to cancer therapy, but suffer from several limitations that restrict their effectiveness in unleashing host immune system components against tumors. The development of monoclonal antibodies of an alternative class, namely IgE, may offer enhanced immune surveillance and superior effector cell potency against cancer cells. In our recent article, we elaborate our proof-of-concept studies of a mouse/human chimeric IgE antibody (MOv18 IgE), which is specific for the cancer-associated antigen folate receptor alpha. We demonstrate superior antitumor efficacy for IgE compared with an otherwise identical IgG in a syngeneic immunocompetent animal, and we identify TNFα/MCP-1 signaling as an IgE-mediated mechanism of monocyte and macrophage activation and recruitment to tumors. These findings draw parallels with powerful macrophage-activating functions employed by IgE against parasites, rather than allergic IgE mechanisms. The potential clinical application of IgE-derived drugs in clinical oncology is clear if the antitumor activity of MOv18 IgE in these preclinical experiments can be replicated in patients. In particular, different IgE antibodies with specificity for many other antigens already validated as targets for IgG suggest a wide potential for development of a novel class of antibody therapy. Cancer Res; 77(11); 2779–83. ©2017 AACR.
Discovery and Optimization of HKT288, a Cadherin-6–Targeting ADC for the Treatment of Ovarian and Renal Cancers
Authors: Bialucha Carl U. , Collins Scott D. , Li Xiao , Saxena Parmita , Zhang Xiamei , Dürr Clemens , Lafont Bruno , Prieur Pierric , Shim Yeonju , Mosher Rebecca , Lee David , Ostrom Lance , Hu Tiancen , Bilic Sanela , Rajlic Ivana Liric , Capka Vladimir , Jiang Wei , Wagner Joel P. , Elliott GiNell , Veloso Artur , Piel Jessica C. , Flaherty Meghan M. , Mansfield Keith G. , Meseck Emily K. , Rubic-Schneider Tina , London Anne Serdakowski , Tschantz William R. , Kurz Markus , Nguyen Duc , Bourret Aaron , Meyer Matthew J. , Faris Jason E. , Janatpour Mary J. , Chan Vivien W. , Yoder Nicholas C. , Catcott Kalli C. , McShea Molly A. , Sun Xiuxia , Gao Hui , Williams Juliet , Hofmann Francesco , Engelman Jeffrey A. , Ettenberg Seth A. , Sellers William R. , Lees Emma
Published: May 2017

Despite an improving therapeutic landscape, significant challenges remain in treating the majority of patients with advanced ovarian or renal cancer. We identified the cell–cell adhesion molecule cadherin-6 (CDH6) as a lineage gene having significant differential expression in ovarian and kidney cancers. HKT288 is an optimized CDH6-targeting DM4-based antibody–drug conjugate (ADC) developed for the treatment of these diseases. Our study provides mechanistic evidence supporting the importance of linker choice for optimal antitumor activity and highlights CDH6 as an antigen for biotherapeutic development. To more robustly predict patient benefit of targeting CDH6, we incorporate a population-based patient-derived xenograft (PDX) clinical trial (PCT) to capture the heterogeneity of response across an unselected cohort of 30 models—a novel preclinical approach in ADC development. HKT288 induces durable tumor regressions of ovarian and renal cancer models in vivo, including 40% of models on the PCT, and features a preclinical safety profile supportive of progression toward clinical evaluation.

Significance: We identify CDH6 as a target for biotherapeutics development and demonstrate how an integrated pharmacology strategy that incorporates mechanistic pharmacodynamics and toxicology studies provides a rich dataset for optimizing the therapeutic format. We highlight how a population-based PDX clinical trial and retrospective biomarker analysis can provide correlates of activity and response to guide initial patient selection for first-in-human trials of HKT288. Cancer Discov; 7(9); 1030–45. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 920
Netrin‐1 Preserves Blood‐Brain Barrier Integrity Through Deleted in Colorectal Cancer/Focal Adhesion Kinase/RhoA Signaling Pathway Following Subarachnoid Hemorrhage in Rats
Authors: Xie Zongyi , Enkhjargal Budbazar , Reis Cesar , Huang Lei , Wan Weifeng , Tang Jiping , Cheng Yuan , Zhang John H.
Published: May 2017

Background

Netrin‐1 (
NTN
‐1) has been established to be a novel intrinsic regulator of blood‐brain barrier (
BBB
) maintenance. This study was carried out to investigate the potential roles of exogenous
NTN
‐1 in preserving
BBB
integrity after experimental subarachnoid hemorrhage (
SAH
) as well as the underlying mechanisms of its protective effects.

Methods and Results

A total of 309 male Sprague‐Dawley rats were subjected to an endovascular perforation model of
SAH
. Recombinant
NTN
‐1 was administered intravenously 1 hour after
SAH
induction.
NTN
‐1 small interfering
RNA
or Deleted in Colorectal Cancer small interfering
RNA
was administered intracerebroventricular at 48 hours before
SAH
. Focal adhesion kinase inhibitor was administered by intraperitoneal injection at 1 hour prior to
SAH
. Neurological scores, brain water content,
BBB
permeability, RhoA activity, Western blot, and immunofluorescence staining were evaluated. The expression of endogenous
NTN
‐1 and its receptor Deleted in Colorectal Cancer were increased after
SAH
. Administration of exogenous
NTN
‐1 significantly reduced brain water content and
BBB
permeability and ameliorated neurological deficits at 24 and 72 hours after
SAH
. Exogenous
NTN
‐1 treatment significantly promoted phosphorylated focal adhesion kinase activation and inhibited RhoA activity, as well as upregulated the expression of
ZO
‐1 and Occludin. Conversely, depletion of endogenous
NTN
‐1 aggravated
BBB
breakdown and neurological impairments at 24 hours after
SAH
. The protective effects of
NTN
‐1 at 24 hours after
SAH
were also abolished by pretreatment with Deleted in Colorectal Cancer small interfering
RNA
and focal adhesion kinase inhibitor.

Conclusions

NTN
‐1 treatment preserved
BBB
integrity and improved neurological functions through a Deleted in Colorectal Cancer/focal adhesion kinase/RhoA signaling pathway after
SAH
. Thus,
NTN
‐1 may serve as a promising treatment to alleviate early brain injury following
SAH
.
T‐Wave Morphology Restitution Predicts Sudden Cardiac Death in Patients With Chronic Heart Failure
Authors: Ramírez Julia , Orini Michele , Mincholé Ana , Monasterio Violeta , Cygankiewicz Iwona , Bayés de Luna Antonio , Martínez Juan Pablo , Pueyo Esther , Laguna Pablo
Published: May 2017

Background

Patients with chronic heart failure are at high risk of sudden cardiac death (
SCD
). Increased dispersion of repolarization restitution has been associated with
SCD
, and we hypothesize that this should be reflected in the morphology of the T‐wave and its variations with heart rate. The aim of this study is to propose an electrocardiogram (
ECG
)‐based index characterizing T‐wave morphology restitution (TMR), and to assess its association with
SCD
risk in a population of chronic heart failure patients.

Methods and Results

Holter
ECG
s from 651 ambulatory patients with chronic heart failure from the
MUSIC
(
MU
erte Súbita en Insuficiencia Cardiaca) study were available for the analysis.
TMR
was quantified by measuring the morphological variation of the T‐wave per
RR
increment using time‐warping metrics, and its predictive power was compared to that of clinical variables such as the left ventricular ejection fraction and other
ECG
‐derived indices, such as T‐wave alternans and heart rate variability.
TMR
was significantly higher in
SCD
victims than in the rest of patients (median 0.046 versus 0.039,
P
<0.001). When
TMR
was dichotomized at
TMR
=0.040, the
SCD
rate was significantly higher in the
TMR
≥0.040 group (
P
<0.001). Cox analysis revealed that
TMR
≥0.040 was strongly associated with
SCD
, with a hazard ratio of 3.27 (
P
<0.001), independently of clinical and
ECG
‐derived variables. No association was found between
TMR
and pump failure death.

Conclusions

This study shows that
TMR
is specifically associated with
SCD
in a population of chronic heart failure patients, and it is a better predictor than clinical and
ECG
‐derived variables.
Factors Associated With Ischemic Stroke Survival and Recovery in Older Adults
Authors: Winovich Divya Thekkethala , Longstreth William T. , Arnold Alice M. , Varadhan Ravi , Zeki Al Hazzouri Adina , Cushman Mary , Newman Anne B. , Odden Michelle C.
Published: May 2017

Background and Purpose—

Little is known about factors that predispose older adults to poor recovery after a stroke. In this study, we sought to evaluate prestroke measures of frailty and related factors as markers of vulnerability to poor outcomes after ischemic stroke.

Methods—

In participants aged 65 to 99 years with incident ischemic strokes from the Cardiovascular Health Study, we evaluated the association of several risk factors (frailty, frailty components, C-reactive protein, interleukin-6, and cystatin C) assessed before stroke with stroke outcomes of survival, cognitive decline (≥5 points on Modified Mini-Mental State Examination), and activities of daily living decline (increase in limitations).

Results—

Among 717 participants with incident ischemic stroke with survival data, slow walking speed, low grip strength, and cystatin C were independently associated with shorter survival. Among participants <80 years of age, frailty and interleukin-6 were also associated with shorter survival. Among 509 participants with recovery data, slow walking speed, and low grip strength were associated with both cognitive and activities of daily living decline poststroke. C-reactive protein and interleukin-6 were associated with poststroke cognitive decline among men only. Frailty status was associated with activities of daily living decline among women only.

Conclusions—

Markers of physical function—walking speed and grip strength—were consistently associated with survival and recovery after ischemic stroke. Inflammation, kidney function, and frailty also seemed to be determinants of survival and recovery after an ischemic stroke. These markers of vulnerability may identify targets for differing pre and poststroke medical management and rehabilitation among older adults at risk of poor stroke outcomes.
Subarachnoid Hemorrhage Severely Impairs Brain Parenchymal Cerebrospinal Fluid Circulation in Nonhuman Primate
Authors: Goulay Romain , Flament Julien , Gauberti Maxime , Naveau Michael , Pasquet Nolwenn , Gakuba Clement , Emery Evelyne , Hantraye Philippe , Vivien Denis , Aron-Badin Romina , Gaberel Thomas
Published: May 2017

Background and Purpose—

Subarachnoid hemorrhage (SAH) is a devastating form of stroke with neurological outcomes dependent on the occurrence of delayed cerebral ischemia. It has been shown in rodents that some of the mechanisms leading to delayed cerebral ischemia are related to a decreased circulation of the cerebrospinal fluid (CSF) within the brain parenchyma. Here, we evaluated the cerebral circulation of the CSF in a nonhuman primate in physiological condition and after SAH.

Methods—

We first evaluated in physiological condition the circulation of the brain CSF in
Macaca
facicularis
, using magnetic resonance imaging of the temporal DOTA-Gd distribution after its injection into the CSF. Then, animals were subjected to a minimally invasive SAH before an MRI evaluation of the impact of SAH on the brain parenchymal CSF circulation.

Results—

We first demonstrate that the CSF actively penetrates the brain parenchyma. Two hours after injection, almost the entire brain is labeled by DOTA-Gd. We also show that our model of SAH in nonhuman primate displays the characteristics of SAH in humans and leads to a dramatic impairment of the brain parenchymal circulation of the CSF.

Conclusions—

The CSF actively penetrates within the brain parenchyma in the gyrencephalic brain, as described for the glymphatic system in rodent. This parenchymal CSF circulation is severely impaired by SAH.
Exacerbation of Thromboinflammation by Hyperglycemia Precipitates Cerebral Infarct Growth and Hemorrhagic Transformation
Authors: Desilles Jean-Philippe , Syvannarath Varouna , Ollivier Véronique , Journé Clément , Delbosc Sandrine , Ducroux Célina , Boisseau William , Louedec Liliane , Di Meglio Lucas , Loyau Stéphane , Jandrot-Perrus Martine , Potier Louis , Michel Jean-Baptiste , Mazighi Mikael , Ho-Tin-Noé Benoit
Published: May 2017

Background and Purpose—

Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury.

Methods—

Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging. Markers of platelet, coagulation, and neutrophil activation were measured in brain homogenates and plasma. Downstream microvascular thromboinflammation (DMT) was investigated by intravital microscopy.

Results—

Hyperglycemic rats had an increased infarct volume with an increased blood–brain barrier disruption and hemorrhagic transformation rate compared with normoglycemic rats. Magnetic resonance imaging scans revealed that hyperglycemia enhanced and accelerated lesion growth and was associated with hemorrhagic transformation originating from territories that were still not completely reperfused at 1 hour after middle cerebral artery recanalization. Intravital microscopy and analysis of brain homogenates showed that DMT began immediately after middle cerebral artery occlusion and was exacerbated by hyperglycemia. Measurement of plasma serotonin and matrix metalloproteinase-9 indicated that platelets and neutrophils were preactivated in hyperglycemic rats. Neutrophils from hyperglycemic diabetic patients showed increased adhesion to endothelial cells as compared with neutrophils from normoglycemic donors in flow chamber experiments.

Conclusions—

We show that hyperglycemia primes the thromboinflammatory cascade, thus, amplifying middle cerebral artery occlusion–induced DMT. DMT exacerbation in hyperglycemic rats impaired reperfusion and precipitated neurovascular damage, blood–brain barrier disruption, and hemorrhagic transformation. Our results designate DMT as a possible target for reduction of the deleterious impact of hyperglycemia in acute ischemic stroke.
Introduction: Revisiting Civil Religion from an Aesthetic Point of View
Authors: Koch Anne
Published: May 2017

This special issue enquires into aesthetic ways of newly creating or re-shaping and re-presenting civil religion and its central characters, symbols, or figures. Normally, civil religion addresses value-orientation and social integration. In addition to these features, the papers make the aesthetic performance of civil religion the subject of discussion. The reason for taking this path is the altered aesthetic circumstances of highly mediatised and consumerist societies. Before this backdrop, images, literary figurations, movie sequences, and brands in media, public and national discourse are examined in various case studies from Italy, Finland, the uk, France, the former gdr, and Switzerland. At the same time, the negotiation and aesthetic plausibility of aesthetic styles, pragmatic power, and particular media logics are evaluated. The concept of civil religion deserves this closer re-definition also with respect to past and recent (post-)secularisation and non-religion discourses. Hopefully, this multi-layered analysis of aesthetics and aesthetic pragmatics of civil religion will shed some light on the persistent appropriateness of the ‘civil religion’ concept and its capacity to be introduced into various methodological contexts in combination with the aesthetic perspective.
Reconfiguring Nationalism: The Roll Call of the Fallen Soldiers (1800–2001)
Authors: Severino Valerio S.
Published: May 2017

Devastating tragedies, such as the 9/11 terrorist attacks or the massacre during the Polish protests of 1970, are still commemorated with a roll call of the victims’ names, which is publicly pronounced. As a matter of civil or political religion, this ritual is studied by political scientists and sociologists and restricted to a specific national context. For the first time, a comparative method of history of religions is applied in order to retrace the transnational diffusion of this nationalist ritual from the Napoleonic era, passing through the fascist European experience, to the present day. The changing of the aesthetic forms in which the ritual took and takes shape, by producing images of the community gathered, outlines an aesthetic realization of ‘imagined communities.’ This outline will be examined with reference to Benedict Anderson’s theory on the origin and spread of nationalism.
State Martyrs: Aesthetics and Performativity of a Contemporary Political Discourse
Authors: Scolari Baldassare
Published: May 2017

The paper focuses on the emergence of national state martyrs in modernity. The investigation postulates a connection between procedures of legitimization of political authority and martyr figurations. It considers martyrological representations as linguistic performances, opening a civil religious space. On the basis of genealogical discourse analysis, the author argues that through secularization the figure of the martyr underwent a transition from the sacral and theological to the profane and political sphere of meaning. In the final part, the paper analyzes the ideological implications of the representation of politician Aldo Moro, killed in 1978 by the Red Brigades, as a state martyr.
Procession as a Literary Motif: The Intersection of Religious and National Symbolism in Italian Narrative (Nineteenth–Twentieth Centuries)
Authors: Ponzo Jenny
Published: May 2017

National imagery developed as a secular substitute for religion, and in modern society, there has been a ‘transfer’ of sacredness from religion to politics. This paper focuses on Italy, where, despite the legal separation of church and state, the ‘sacral’ national apparatus still owes a considerable debt to religion. After a short exposition of some of the main theories of civil religion in Italy, this work will analyze a corpus of Italian novels set during the Risorgimento, a period that functions in Italian culture as an atypical founding myth. It will show in particular how civil and religious symbols and rituals intersect in the literary representation of processions. Indeed, the procession is a recurring motif in Italian narrative and presents peculiar aesthetic features. The analysis of this literary motif will take advantage of socio-anthropological theories and will trace a distinction between ordered and disordered, or enthusiastic, processions.
Religious in Form, Socialist in Content: Socialist Narratives and the Question of Civil Religion
Authors: Kirsch Anja
Published: May 2017

Socialist narratives have a long history of being interpreted as religious in content and form. Scholars draw on concepts such as ‘political religion,’ ‘secular religion,’ and ‘civil religion’ to describe an alleged world-transcending quality of socialism. These concepts possess, however, normative implications since they often suggest a difference from ‘true’ or ‘real’ religion. The following article does not select a specific definition to confirm or repudiate the alleged character of socialism as a civil religion; nor will it suggest another term to describe this character more appropriately. Instead, it addresses the as-religion reflex evidenced in such acts of classification themselves by asking the question: what are the aesthetic conditions for a political system to be perceived as religious? By analysing various implementation strategies of the German Democratic Republic’s master narrative—captured in the motto “socialism will triumph”—this paper examines the narrative structures through which real socialism produced meaning. Literary-aesthetic analysis reveals that meaning and relevance were created through a carefully selected set of literary patterns. These patterns can induce the as-religion reflex even when the narrative content is considered to be secular. Reflections and analytical differentiations of form and content prove crucial to classifying narratives as expressions of civil religion.
An Unexpected Overlap between Civil Religion and Consumption: The Unseen Role of Conscious Commodity Design
Authors: Ulrich Michael
Published: May 2017

This paper argues that the societally homogenising function attributed to civil religion possibly has, at least in parts, been assumed by conscious commodity design. Inasmuch as conscious commodity design helps to promote consumption, it is argued, it is potentially conducive to the achievement of a satisfactory level of economic growth, which is considered a national goal in many countries. In this trajectory of argumentation, the role played by aesthetics, or, more specifically, by the consumer’s aesthetic experience therein is moved to the foreground and explored with a small socio-empirical experiment. Based on the findings, a thesis regarding the normative power of conscious commodity design with respect to a normalising of sensory orders in consumers is formulated. Its implications for consumer judgement, notably limiting and determining the consumer’s reality-making, are discussed.
Energy Spectra and Inertia–Gravity Waves in Global Analyses
Authors: Žagar Nedjeljka , Jelić Damjan , Blaauw Marten , Bechtold Peter
Published: May 2017

Several decades after E. Dewan predicted that the shallowing of the atmospheric energy spectrum in mesoscale is produced by the inertia–gravity (IG) waves, global analyses have reached the resolution at which the IG waves across many scales are resolved. The authors discuss the spatial filtering method based on the Hough harmonics that provides the temperature and wind perturbations associated with the IG waves in global analysis data. The method is applied to the ECMWF interim reanalysis and the operational 2014–16 analysis fields. The derived spectrum of IG wave energy is divided into three regimes: a part associated with the large-scale unbalanced circulations that has a slope close to −1 for zonal wavenumbers 1 ≤ k ≤ 6, a synoptic-scale range between 3000 and around 500 km (7 ≤ k ≲ 35) that is characterized by a nearly −5/3 slope, and a mesoscale range below 500 km where the slope of the IG energy spectrum in the 2015/16 analyses is steeper. In contrast, the energy spectrum of the Rossby waves has a −3 slope for all zonal wavenumbers k > 6. Presented results suggest that energy associated with the IG modes exceeds the level of energy associated with the Rossby waves around zonal wavenumber 35. The exact wavenumber depends on the season and considered atmospheric depth and it is suggested as a cutoff scale for studies of gravity waves.
Predictive Validity and Impact of CAEP Standard 3.2: Results From One Master’s-Level Teacher Preparation Program
Authors: Evans Carla M.
Published: May 2017

This study investigates the predictive validity and policy impact of Council for Accreditation of Educator Preparation minimum admission requirements in Standard 3.2 on teacher preparation programs (TPPs), their applicants, and the broader field of educator preparation. Undergraduate grade point average (GPA) and Graduate Record Examination (GRE) scores from 533 program graduates in one master’s-level TPP were examined for their ability to predict graduate GPA and the effect minimum admissions criteria had on enrollment. Findings indicate that only undergraduate GPA is moderately related to a program graduate’s success, controlling for student background characteristics. The study also finds that implementing GRE scores as a criterion in admissions decisions significantly reduces the number of admitted candidates so that the program may no longer be financially sustainable. These findings suggest many negative consequences may result from minimum admission requirements and more research is needed to evaluate the potential impact on other TPPs, teacher labor markets, and student learning outcomes.
State capacity and the resilience of electoral authoritarianism: Conceptualizing and measuring the institutional underpinnings of autocratic power
Authors: Hanson Jonathan K
Published: May 2017

This article discusses three main challenges to gaining a better understanding of whether state capacity contributes to the resilience of electoral authoritarian regimes. First, the concept of state capacity is multi-dimensional and can be entangled with regime organizational structures. Second, there is a range of different mechanisms through which elections may draw upon capacity in these different dimensions to affect authoritarian resilience. Third, good indicators of the dimensions of state capacity for empirical work are sorely lacking. To address these challenges, this article outlines the connections between extractive, coercive and administrative dimensions of state capacity with regard to how electoral authoritarian regimes address threats arising from society and from within the ruling elite. It then assesses different approaches to measuring these dimensions for empirical work.
Deep analysis of wind variability and smoothing effect in Moroccan wind farms
Authors: Choukri Karim , Naddami Ahmed , Hayani Sanaa Mounir
Published: May 2017

The Moroccan energy strategy has set new targets of reaching 52% of installed renewable energy capacity by 2030, through the development of renewable energy, including solar and wind energy. The massive use of renewables leads the country to deal with its intermittency and improve its integration in the grid. The offset between wind farms generation in different regions is essential for quantifying the reduction of intermittency when we chose wind farms sites. This offset, the smoothing effect, is analyzed deeply in this article to evaluate different compensation zones. Six wind farms with wind power variability and their potential impact on the capacity reserve are presented. The site’s power was generated from reel hourly data during 12 months. Results show that energy fluctuation depends on typical wind regimes and the capacity of farms. North wind farms (280 MW) produce 50% of the maximum during 43% of time and south wind farms produce it only 17% of time. The first farm’s power consistently spreads more than south farms, but also more smoothed. The average intermittency reduced as farm capacity increased due to the turbine smoothing effect and the reserve requirements increased on average. The behavior of south wind farms is more correlated, then the backup needed will be less.
Reconstructing absolute water-level variability of Lake Prespa (SW Balkans) during the Medieval Climate Anomaly and ‘Little Ice Age’ from a prograding beach ridge complex
Authors: van der Schriek Tim , Giannakopoulos Christos
Published: May 2017

Lake Prespa beach ridges register climate-driven water-level fluctuations that contain a strong North Atlantic signal. This study examines the beach ridge complex that underlies the Koula isthmus (Lake Prespa, Greece) and contains a sedimentary archive of lake-level variations spanning >5 kyr. Past lake levels were reconstructed through the accurate height survey of selected beach sediment facies that form reliable stage indicators. Here, we present the first quantitative lake level recorded in the Balkans, covering ~1 kyr, based on sediment-stratigraphic analyses and supported by five radiocarbon and six optically stimulated luminescence (OSL) age estimates. All major low/high lake phases over the past millennium were identified and dated in the sediment record. Low lake levels (842–847 m) from AD 900–1000 to AD 1430 dominated the Medieval Climate Anomaly (MCA). Generally, high water levels (>847 m) are recorded after AD ~1430, corresponding to the regional start of the ‘Little Ice Age’ (LIA), up to AD 1987. This high lake phase was interspersed by a multi-decadal water-level fall to ~846.5 m ending AD ~1650. Low levels after AD 1987 (842–845 m) were mainly caused by water abstraction. Absolute water-level changes in Lake Prespa over the past millennium mirror the pattern of hydro-climatic changes in the west-central Mediterranean, indicating that the study region belonged to this hydro-climatic domain. The observed influence of the North Atlantic Oscillation (NAO) on winter precipitation and lake level (1951–2004) is also relevant over the past ~1 kyr, as the NAO index was overall positive during the MCA and negative during the ‘LIA’.
Necessity of Immobilizing the Metacarpophalangeal Joint in Carpometacarpal Osteoarthritis: Short-term Effect
Authors: Cantero-Téllez Raquel , Valdes Kristin , Schwartz Deborah A. , Medina-Porqueres Ivan , Arias Jean Christophe , Villafañe Jorge H.
Published: May 2017

Background: Conservative treatment for carpometacarpal (CMC) joint osteoarthritis (OA) may include orthotic fabrication to decrease pain. Different types of orthoses have been used as conservative interventions to improve symptoms, but there are no guidelines specifying if inclusion of the thumb metacarpophalangeal (MCP) in an orthosis is required in the treatment of thumb CMC joint OA. The main objective of this study is to determine the effectiveness of 2 different thumb CMC joint orthotic designs on pain reduction and improved hand function: one design immobilizes both the MCP joint and the CMC joint and the other design immobilizes only the CMC joint. Methods: A total of 66 patients were included in the study. One group of 33 patients received a short thumb orthosis with the MCP joint excluded, and the other group of 33 patients received a short thumb orthosis with the MCP joint included. Outcomes measures included the visual analog scale for pain and the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH; Spanish version) for function. Results: In both patient groups, the orthoses contributed to decreased pain levels and improved functional abilities ( F1.0 = 315.467 and F1.0 = 72.419; both, P < .001). There was no significant difference between the 2 groups regarding pain or improvement in daily activities ( F1.0 = 0.553 and F1.0 = 2.539; both, P > .05). Conclusion: There are benefits of either thumb orthotic design on pain reduction and functional improvement even after 1 week of using the orthoses as the sole conservative treatment.
Student Attitudes Toward Poverty in a Social Welfare Policy Course: Online Versus Face to Face
Authors: Hamilton Leah , Daughtry Lindsay
Published: May 2017

The growth of online higher education has presented important questions for social workers in academia. Can a human-based profession be properly taught online? In macro courses, are social work students able to gain a complex understanding of human experience, social justice, and oppression without the benefit of face-to-face debate and dialogue? In an undergraduate social welfare policy course, pre and post anonymous opinions surveys were collected on the causes of poverty. Students in both a face-to-face and an online course section, were asked to rate their agreement with the statements “Poverty is usually caused by individual actions” and “Poverty is usually caused by societal actions.” While no statistically significant changes appeared for face-to-face students, online students were more likely to decrease blame for individual actions and increased attribution for societal actions at posttest. Reasons for this difference will be discussed, including the possible role of peer influence in face-to-face course sessions.
Cold agglutinin disease burden: a longitudinal analysis of anemia, medications, transfusions, and health care utilization
Authors: Mullins Megan , Jiang Xiaohui , Bylsma Lauren C. , Fryzek Jon P. , Reichert Heidi , Chen Evan C. , Kummar Shivaani , Rosenthal Adam
Published: May 2017

Key Points

This study demonstrates the severity of anemia and relapsing nature of CAD over time, even after administration of multiple therapies. The majority of CAD patients will at some point in their disease course manifest severe disease necessitating transfusion.
Long-lived plasma cells in human bone marrow can be either CD19+ or CD19–
Authors: Brynjolfsson Siggeir F. , Mohaddes Maziar , Kärrholm Johan , Wick Mary-Jo
Published: May 2017

Key Points

Long-lived plasma cells secreting vaccinia-specific antibodies are detected in human bone marrow >35 years after the eradication of smallpox. Long-lived plasma cells secreting vaccinia-specific antibodies are still able to express the B-lymphocyte antigen CD19.
Smoking, alcohol and drug use in youth and adults with attention-deficit hyperactivity disorder
Authors: Osland Sydney , Hirsch Lauren , Pringsheim Tamara
Published: May 2017

Background

Previous research suggests a relationship between attention-deficit hyperactivity disorder (ADHD) and smoking, alcohol and illicit drug use, however most studies have focused on adolescents or young adults, or clinically ascertained samples.

Aims

To analyse population-based data on the relationship between ADHD and at-risk health behaviours in adolescents and adults.

Method

Data were derived from a Statistics Canada population-based health survey. The association between the diagnosis of ADHD and smoking, alcohol use, and illicit drug use was examined.

Results

Individuals with ADHD started smoking at a younger age. They consumed more alcoholic drinks on drinking days, and women with ADHD were more likely to engage in binge drinking. Women over the age of 25 and men with ADHD were more likely to meet alcohol-dependence lifetime criteria. People with ADHD were at a greater risk of drug misuse and dependence.

Conclusions

People with ADHD are more likely to partake in at-risk behaviours.
Subcellular Energetics and Metabolism: A Cross-Species Framework
Authors: Thiele Robert H.
Published: May 2017

Although it is generally believed that oxidative phosphorylation and adequate oxygenation are essential for life, human development occurs in a profoundly hypoxic environment and “normal” levels of oxygen during embryogenesis are even harmful. The ability of embryos not only to survive but also to thrive in such an environment is made possible by adaptations related to metabolic pathways. Similarly, cancerous cells are able not only to survive but also to grow and spread in environments that would typically be fatal for healthy adult cells. Many biological states, both normal and pathological, share underlying similarities related to metabolism, the electron transport chain, and reactive species. The purpose of Part I of this review is to review the similarities among embryogenesis, mammalian adaptions to hypoxia (primarily driven by hypoxia-inducible factor-1), ischemia-reperfusion injury (and its relationship with reactive oxygen species), hibernation, diving animals, cancer, and sepsis, with a particular focus on the common characteristics that allow cells and organisms to survive in these states.
Thoracic Epidural Analgesia With Levobupivacaine Reduces Remifentanil and Propofol Consumption Evaluated by Closed-Loop Titration Guided by the Bispectral Index: A Double-Blind Placebo-Controlled Study
Authors: Dumans-Nizard Virginie , Le Guen Morgan , Sage Edouard , Chazot Thierry , Fischler Marc , Liu Ngai
Published: May 2017

BACKGROUND:

Thoracic epidural analgesia (TEA) combined with general anesthesia decreases anesthetic requirements by half when hemodynamic criteria are used for the titration of analgesia. We therefore determined the impact of TEA on anesthetic requirements, when a closed-loop controller was used allowing the automated coadministration of propofol-remifentanil guided solely by the Bispectral index.

METHODS:

This single-center double-blind study enrolled patients scheduled for elective posterolateral thoracotomy using TEA. Patients were randomly assigned to receive a bolus followed by a continuous infusion of levobupivacaine 0.5% (levo group) or saline 0.9% solution (saline group). General anesthesia was performed by the same automated controller. Stroke volume optimization guided by an esophageal Doppler probe was performed before randomization. The primary outcome variable was the amount of remifentanil delivered by the automated controller between skin incision and closure. Major arterial hypotension was recorded. Data are presented as medians [interquartile range] or number (%)

RESULTS:

Nineteen adult patients per group completed the study. At similar depth of anesthesia evaluated by the percentage of time with the Bispectral index in the range 40–60 (85 [77–88] vs 83 [72–87]; P = .39), patients with neuraxial block required less remifentanil (0.15 [0.10–0.20] vs 0.23 [0.14–0.25], µg·kg−
1·min−
1; P = .03) and propofol (4.3 [3.7–4.9] vs 5.7 [4.6–7.3] mg·kg−
1·h−1; P = .005). Major arterial hypotension was similar in both groups (6 [32%] vs 5 [25%]; P = .46; levo versus saline group, respectively).

CONCLUSIONS:

Epidurally administered levobupivacaine allowed a decrease by one-third of remifentanil requirement. After stroke volume optimization, major arterial hypotension was similar between groups.
Perineural Dexmedetomidine Is More Effective Than Clonidine When Added to Local Anesthetic for Supraclavicular Brachial Plexus Block: A Systematic Review and Meta-analysis
Authors: El-Boghdadly Kariem , Brull Richard , Sehmbi Herman , Abdallah Faraj W.
Published: May 2017

BACKGROUND:

Clonidine, an α-2 agonist, has long been used as a local anesthetic adjunct with proven efficacy to prolong peripheral nerve block duration. Dexmedetomidine, a newer α-2 agonist, has a more favorable pharmacodynamic and safety profile; however, data comparing its efficacy as an adjunct to that of clonidine are inconsistent. We sought to compare the clinical efficacy of these 2 α-2 agonists by examining their effects on peripheral nerve block characteristics for upper extremity surgery.

METHODS:

A preliminary search found that the overwhelming majority of randomized controlled trials comparing perineural dexmedetomidine to clonidine for upper extremity surgery were in the setting of supraclavicular brachial plexus block (SCB). Therefore, we performed a systematic review and meta-analysis of randomized controlled trials comparing dexmedetomidine with clonidine as perineural adjuncts to single-injection SCB. Sensory and motor block duration and onset, analgesic duration, α-2 agonist side effects, and block complications were analyzed. Sensory block duration was designated as a primary outcome. Data were combined using random-effects modeling, and ratio-of-means was used to analyze the results.

RESULTS:

A total of 868 patients from 14 clinical studies were included in the analysis. Compared with clonidine, dexmedetomidine prolonged the duration (ratio of means [95% confidence interval {CI}]) of sensory block by an estimate of 1.2 (1.2–1.3; P< .00001). It also prolonged the duration (ratio of means [99% CI]) of motor block by an estimate of 1.2 (1.1–1.3; P < .00001), and analgesia by an estimate of 1.2 (1.1–1.3; P < .00001). It also hastened the onset of sensory block by an estimate of 0.9 (0.8–1.0; P < .00001) and motor block by an estimate of 0.9 (0.9–1.0; P = .002). Dexmedetomidine was associated with an increased odds ratio (99% CI) of transient bradycardia by an estimate of 7.4 (1.3–40.8; P = .003) and postoperative sedation by an estimate of 11.8 (1.9–73.6; P = .0005). There were no differences in other α-2 agonist–related side effects or block-related complications.

CONCLUSIONS:

Compared with clonidine as a local anesthetic adjunct for single-injection SCB, perineural dexmedetomidine enhances sensory, motor, and analgesic block characteristics. These benefits should be weighed against the increased risk of transient bradycardia.
Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery
Authors: Mauermann Eckhard , Bolliger Daniel , Fassl Jens , Grapow Martin , Seeberger Esther E. , Seeberger Manfred D. , Filipovic Miodrag , Lurati Buse Giovanna A. L.
Published: May 2017

BACKGROUND:

Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality.

METHODS:

We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality.

RESULTS:

We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014–1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007–1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754–0.878] versus area under curve: 0.870 [95% confidence interval, 0.822–0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events.

CONCLUSIONS:

This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.
Zika Virus: Obstetric and Pediatric Anesthesia Considerations
Authors: Tutiven Jacqueline L. , Pruden Benjamin T. , Banks James S. , Stevenson Mario , Birnbach David J.
Published: May 2017

As of November 2016, the Florida Department of Health (FDH) and the Centers for Disease Control and Prevention have confirmed more than 4000 travel-related Zika virus (ZIKV) infections in the United States with >700 of those in Florida. There have been 139 cases of locally acquired infection, all occurring in Miami, Florida. Within the US territories (eg, Puerto Rico, US Virgin Islands), >30,000 cases of ZIKV infection have been reported. The projected number of individuals at risk for ZIKV infection in the Caribbean and Latin America approximates 5 million. Similar to Dengue and Chikungunya viruses, ZIKV is spread to humans by infected Aedes aegypti mosquitoes, through travel-associated local transmission, via sexual contact, and through blood transfusions. South Florida is an epicenter for ZIKV infection in the United States and the year-round warm climate along with an abundance of mosquito vectors that can harbor the flavivirus raise health care concerns. ZIKV infection is generally mild with clinical manifestations of fever, rash, conjunctivitis, and arthralgia. Of greatest concern, however, is growing evidence for the relationship between ZIKV infection of pregnant women and increased incidence of abnormal pregnancies and congenital abnormalities in the newborn, now medically termed ZIKA Congenital Syndrome. Federal health officials are observing 899 confirmed Zika-positive pregnancies and the FDH is currently monitoring 110 pregnant women with evidence of Zika infection. The University of Miami/Jackson Memorial Hospital is uniquely positioned just north of downtown Miami and within the vicinity of Liberty City, Little Haiti, and Miami Beach, which are currently “hot spots” for Zika virus exposure and transmissions. As the FDH works fervently to prevent a Zika epidemic in the region, health care providers at the University of Miami and Jackson Memorial Hospital prepare for the clinical spectrum of ZIKV effects as well as the safe perioperative care of the parturients and their affected newborns. In an effort to meet anesthetic preparedness for the care of potential Zika-positive patients and perinatal management of babies born with ZIKA Congenital Syndrome, this review highlights the interim guidelines from the Centers for Disease Control and Prevention and also suggest anesthetic implications and recommendations. In addition, this article reviews guidance for the evaluation and anesthetic management of infants with congenital ZIKV infection. To better manage the perioperative care of affected newborns, this article also reviews the comparative anesthetic implications of babies born with related congenital malformations.
Development of Education and Research in Anesthesia and Intensive Care Medicine at the University Teaching Hospital in Lusaka, Zambia: A Descriptive Observational Study
Authors: Janowicz Anna , Kasole Tuma , Measures Emily , Langley Meg , Goma Fastone M. , Ismailova Feruza , Kinnear John A. , Bould M. Dylan
Published: May 2017

BACKGROUND:

Data from 2006 show that the practice of anesthesia at the University Teaching Hospital in Lusaka, Zambia was underdeveloped by international standards. Not only was there inadequate provision of resources related to environment, equipment, and drugs, but also a severe shortage of staff, with no local capability to train future physician anesthetic providers. There was also no research base on which to develop the specialty. This study aimed to evaluate patient care, education and research to determine whether conditions had changed a decade later.

METHODS:

A mix of qualitative data and quantitative data was gathered to inform the current state of anesthesia at the University Teaching Hospital, Lusaka, Zambia. Semistructured interviews were conducted with key staff identified by purposive sampling, including staff who had worked at the hospital throughout 2006 to 2015. Further data detailing conditions in the environment were collected by reviewing relevant departmental and hospital records spanning the study period. All data were analyzed thematically, using the framework described in the 2006 study, which described patient care, education, and research related to anesthetic practice at the hospital.

RESULTS:

There have been positive developments in most areas of anesthetic practice, with the most striking being implementation of a postgraduate training program for physician anesthesiologists. This has increased physician anesthesia staff in Zambia 6-fold within 4 years, and created an active research stream as part of the program. Standards of monitoring and availability of drugs have improved, and anesthetic activity has expanded out of operating theaters into the rest of the hospital. A considerable increase in the number of cesarean deliveries performed under spinal anesthetic may be a marker for safer anesthetic practice. Anesthesiologists have yet to take responsibility for the management of pain.

CONCLUSIONS:

The establishment of international partnerships to support postgraduate training of physician anesthetists in Zambia has created a significant increase in the number of anesthesia providers and has further developed nearly all aspects of anesthetic practice. The facilitation of the training program by a global health partnership has leveraged high-level support for the project and provided opportunities for North-South and international learning.