bluuebunny/crossref_metadata_2025 huggingface dataset:
A Path Forward for Regenerative Medicine
Authors: Fanaroff Alexander C. , Morrow Valarie , Krucoff Mitchell W. , Seltzer Jonathan H. , Perin Emerson C. , Taylor Doris A. , Miller Leslie W. , Zeiher Andreas M. , Fernández-Avilés Francisco , Losordo Douglas W. , Henry Timothy D. , Povsic Thomas J.
Published: September 2018

Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval and identify strategies to facilitate this goal, the Cardiac Safety Research Consortium sponsored a session during the Texas Heart Institute International Symposium on Cardiovascular Regenerative Medicine in September 2017. This session convened leaders in cardiovascular regenerative medicine, including participants from academia, the pharmaceutical industry, the US Food and Drug Administration, and the Cardiac Safety Research Consortium, with particular focus on treatments closest to regulatory approval. A goal of the session was to identify barriers to regulatory approval and potential pathways to overcome them. Barriers identified include manufacturing and therapeutic complexity, difficulties identifying an optimal comparator group, limited industry capacity for funding pivotal clinical trials, and challenges to demonstrating efficacy on clinical end points required for regulatory decisions. Strategies to overcome these barriers include precompetitive development of a cell therapy registry network to enable dual-purposing of clinical data as part of pragmatic clinical trial design, development of standardized terminology for product activity and end points to facilitate this registry, use of innovative statistical methods and quality of life or functional end points to supplement outcomes such as death or heart failure hospitalization and reduce sample size, involvement of patients in determining the research agenda, and use of the Food and Drug Administration’s new Regenerative Medicine Advanced Therapy designation to facilitate early discussion with regulatory authorities when planning development pathways.
Reassessing the Role of Surrogate End Points in Drug Development for Heart Failure
Authors: Greene Stephen J. , Mentz Robert J. , Fiuzat Mona , Butler Javed , Solomon Scott D. , Ambrosy Andrew P. , Mehta Cyrus , Teerlink John R. , Zannad Faiez , O’Connor Christopher M.
Published: September 2018

With few notable exceptions, drug development for heart failure (HF) has become progressively more challenging, and there remain no definitively proven therapies for patients with acute HF or HF with preserved ejection fraction. Inspection of temporal trends suggests an increasing rate of disagreement between early-phase and phase III trial end points. Preliminary results from phase II HF trials are frequently promising, but increasingly followed by disappointing phase III results. Given this potential disconnect, it is reasonable to carefully re-evaluate the purpose, design, and execution of phase II HF trials, with particular attention directed toward the surrogate end points commonly used by these studies. In this review, we offer a critical reappraisal of the role of phase II HF trials and surrogate end points, highlighting challenges in their use and interpretation, lessons learned from past experiences, and specific strengths and weaknesses of various surrogate outcomes. We conclude by proposing a series of approaches that should be considered for the goal of optimizing the efficiency of HF drug development. This review is based on discussions between scientists, clinical trialists, industry and government sponsors, and regulators that took place at the Cardiovascular Clinical Trialists Forum in Washington, DC, on December 2, 2016.
Discordant Alternans as a Mechanism for Initiation of Ventricular Fibrillation In Vitro
Authors: Muñoz Laura M. , Gelzer Anna R. M. , Fenton Flavio H. , Qian Wei , Lin WeiYe , Gilmour Robert F. , Otani Niels F.
Published: September 2018

Background

Ventricular tachyarrhythmias are often preceded by short sequences of premature ventricular complexes. In a previous study, a restitution‐based computational model predicted which sequences of stimulated premature complexes were most likely to induce ventricular fibrillation in canines in vivo. However, the underlying mechanism, based on discordant‐alternans dynamics, could not be verified in that study. The current study seeks to elucidate the mechanism by determining whether the spatiotemporal evolution of action potentials and initiation of ventricular fibrillation in in vitro experiments are consistent with model predictions.

Methods and Results

Optical mapping voltage signals from canine right‐ventricular tissue (n=9) were obtained simultaneously from the entire epicardium and endocardium during and after premature stimulus sequences. Model predictions of action potential propagation along a 1‐dimensional cable were developed using action potential duration versus diastolic interval data. The model predicted sign‐change patterns in action potential duration and diastolic interval spatial gradients with posterior probabilities of 91.1%, and 82.1%, respectively. The model predicted conduction block with 64% sensitivity and 100% specificity. A generalized estimating equation logistic‐regression approach showed that model‐prediction effects were significant for both conduction block (
P
<1×10
−15
, coefficient 44.36) and sustained ventricular fibrillation (
P
=0.0046, coefficient, 1.63) events.

Conclusions

The observed sign‐change patterns favored discordant alternans, and the model successfully identified sequences of premature stimuli that induced conduction block. This suggests that the relatively simple discordant‐alternans‐based process that led to block in the model may often be responsible for ventricular fibrillation onset when preceded by premature beats. These observations may aid in developing improved methods for anticipating block and ventricular fibrillation.
Advanced Practice Provider Versus Physician‐Only Outpatient Follow‐Up After Acute Myocardial Infarction
Authors: Rymer Jennifer A. , Chen Anita Y. , Thomas Laine , Stafford Judith , Enriquez Jonathan R. , Goyal Abhinav , Peterson Eric D. , Wang Tracy Y.
Published: September 2018

Background

Physician shortages and reimbursement changes have led to greater use of advanced practice providers (
APP
s). Prevalence of and outcomes associated with
APP
care following myocardial infarction are unknown.

Methods and Results

We examined outpatient cardiology or primary care visits within 90 days post‐myocardial infarction among 29 477 Medicare‐insured patients aged ≥65 years from 364 hospitals in Acute Coronary Treatment Intervention Outcomes Network Registry. We compared medication adherence, all‐cause readmission risk, mortality, and major adverse cardiovascular events between patients seen by
APP
s versus physicians only. Overall, 11% of myocardial infarction patients were treated by an
APP
. Patients seen by
APP
s were more likely to have diabetes mellitus (37% versus 33%) and heart failure (20% versus 16%), be discharged to a nursing facility (21% versus 13%) and had more outpatient visits within 90 days post‐discharge (median 6 versus 5,
P
<0.01 for all) than those seen by physicians only. Adherence to evidence‐based medications (adjusted odds ratio, 0.98; 95% confidence interval, 0.89–1.08) and readmission risks (adjusted hazard ratio, 1.11; 95% confidence interval, 0.99–1.26) were similar between patients seen by
APP
s versus physicians only. Risks of 90‐day mortality (adjusted hazard ratio, 1.18; 95% confidence interval, 0.98–1.42) and major adverse cardiovascular events (adjusted hazard ratio, 1.06; 95% confidence interval, 0.90–1.23) were also similar between patients seen by
APP
s versus physicians only.

Conclusions

APP
s were likely used to provide more frequent monitoring of high‐risk post‐
MI
patients. Medication adherence, readmission risk, mortality, and major adverse cardiovascular events did not differ substantially between patients seen by physician‐
APP
teams than those seen by physicians only.
Phase Angle as a Biomarker for Frailty and Postoperative Mortality: The BICS Study
Authors: Mullie Louis , Obrand Alexandrine , Bendayan Melissa , Trnkus Amanda , Ouimet Marie‐Claude , Moss Emmanuel , Chen‐Tournoux Annabel , Rudski Lawrence G. , Afilalo Jonathan
Published: September 2018

Background

Phase angle (PA) is a bioimpedance measurement that is determined lean body mass and hydration status. Patients with low PA values are more likely to be frail, sarcopenic, or malnourished. Previous work has shown that low PA predicts adverse outcomes after cardiac surgery, but the effect of PA on survival has not previously been assessed in this setting.

Methods and Results

The BICS (Bioimpedance in Cardiac Surgery) study recruited 277 patients undergoing major cardiac surgery at 2 university‐affiliated hospitals in Montreal, QC, Canada. Bioimpedance measurements as well as frailty and nutritional assessments were performed preoperatively. The primary outcome was all‐cause mortality. Secondary outcomes were 30‐day mortality, postoperative morbidity, and hospital length of stay. There were 10 deaths at 1 month of follow‐up and 16 deaths at 12 months of follow‐up.
PA
was associated with age, sex, body mass index, comorbidities, and frailty, as measured by the Short Physical Performance Battery and Fried scales. After adjusting for Society of Thoracic Surgeons–predicted mortality, lower
PA
was associated with higher mortality at 1 month (adjusted odds ratio, 3.57 per 1° decrease in
PA
; 95% confidence interval, 1.35–9.47) and at 12 months (adjusted odds ratio, 3.03 per 1° decrease in
PA
; 95% confidence interval, 1.30–7.09), a higher risk of overall morbidity (adjusted hazard ratio, 2.51 per 1° decrease in
PA
; 95% confidence interval, 1.32–4.75), and a longer hospital length of stay (adjusted β, 4.8 days per 1° decrease in
PA
; 95% confidence interval, 1.3–8.2 days).

Conclusions

Low
PA
is associated with frailty and is predictive of mortality, morbidity, and length of stay after major cardiac surgery. Further work is needed to determine the responsiveness of
PA
to interventions aimed at reversing frailty.
Pharmacotherapy for Atrial Fibrillation in Patients With Chronic Kidney Disease: Insights From ORBIT‐AF
Authors: Washam Jeffrey B. , Holmes DaJuanicia N. , Thomas Laine E. , Pokorney Sean D. , Hylek Elaine M. , Fonarow Gregg C. , Mahaffey Kenneth W. , Gersh Bernard J. , Kowey Peter R. , Ansell Jack E. , Go Alan S. , Reiffel James A. , Freeman James V. , Singer Daniel E. , Naccarelli Gerald , Blanco Rosalia , Peterson Eric D. , Piccini Jonathan P.
Published: September 2018

Background

Chronic kidney disease (
CKD
) is a common comorbidity in patients with atrial fibrillation. The presence of
CKD
complicates drug selection for stroke prevention and rhythm control.

Methods and Results

Patients enrolled in ORBIT AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) with baseline renal function and follow‐up data were included (N=9019).
CKD
was defined as an estimated creatinine clearance <60
mL
/min. Patient characteristics were compared by
CKD
status, and Cox proportional hazards modeling was used to examine the association between oral anticoagulant (
OAC
) use and outcomes and antiarrhythmic drug use and outcomes stratified by
CKD
stages. At enrollment, 3490 (39%) patients had an estimated creatinine clearance <60
mL
/min. Patients with
CKD
were older and had higher
CHA
2
DS
2
VAS
c and Anticoagulant and Risk Factors in Atrial Fibrillation (ATRIA) scores. A rhythm control strategy was selected less frequently in patients with
CKD
, while
OAC
use was lower among Stage
IV
and V
CKD
patients. After adjustment, no significant interaction was noted for
OAC
and
CKD
on all‐cause mortality (
P
=0.5442) or cardiovascular death (
P
=0.1233), although a trend for increased major bleeding (
P
=0.0608) and stroke, systemic embolism or transient ischemic attack (
P
=0.0671) was observed. No interaction was noted for antiarrhythmic drug use and
CKD
status on all‐cause mortality (
P
=0.9706), or stroke, systemic embolism or transient ischemic attack (
P
=0.4218).

Conclusions

Patients with atrial fibrillation and
CKD
are less likely to be treated with rhythm control. Patients with advanced
CKD
are less likely to receive
OAC
. Finally, outcomes with
OAC
in patients with advanced
CKD
may be materially different with higher rates of both bleeding and stroke.
Primary Effect of SERCA2a Gene Transfer on Conduction Reserve in Chronic Myocardial Infarction
Authors: Motloch Lukas J. , Cacheux Marine , Ishikawa Kiyotake , Xie Chaoqin , Hu Jun , Aguero Jaume , Fish Kenneth M. , Hajjar Roger J. , Akar Fadi G.
Published: September 2018

Background

SERCA
2a gene transfer (
GT
) improves mechano‐electrical function in animal models of nonischemic heart failure Whether
SERCA
2a
GT
reverses pre‐established remodeling at an advanced stage of ischemic heart failure is unclear. We sought to uncover the electrophysiological effects of adeno‐associated virus serotype 1.
SERCA
2a
GT
following myocardial infarction (
MI
).

Methods and Results

Pigs developed mechanical dysfunction 1 month after anterior
MI
, at which point they received intracoronary adeno‐associated virus serotype 1.
SERCA
2a (
MI
+
SERCA
2a) or saline (
MI
) and were maintained for 2 months. Age‐matched naive pigs served as controls (Control). In vivo
ECG
‐and‐hemodynamic properties were assessed before and after dobutamine stress. The electrophysiological substrate was measured using optical action potential (
AP
) mapping in controls,
MI
, and
MI
+
SERCA
2a preparations. In vivo
ECG
measurements revealed comparable
QT
durations between groups. In contrast, prolonged
QRS
duration and increased frequency of R′ waves were present in
MI
but not
MI
+
SERCA
2a pigs relative to controls.
SERCA
2a
GT
reduced in in vivo arrhythmias in response to dobutamine. Ex vivo preparations from
MI
but not
MI
+
SERCA
2a or control pigs were prone to pacing‐induced ventricular tachycardia and fibrillation. Underlying these arrhythmias was pronounced conduction velocity slowing in
MI
versus
MI
+
SERCA
2a at elevated rates leading to ventricular tachycardia and fibrillation. Reduced susceptibility to ventricular tachycardia and fibrillation in
MI
+
SERCA
2a pigs was not related to hemodynamic function, contractile reserve, fibrosis, or the expression of Cx43 and Nav1.5. Rather,
SERCA
2a
GT
decreased phosphoactive
CAMKII
‐delta levels by >50%, leading to improved excitability at fast rates.

Conclusions

SERCA
2a
GT
increases conduction velocity reserve, likely by preventing
CAMKII
overactivation. Our findings suggest a primary effect of
SERCA
2a
GT
on myocardial excitability, independent of altered mechanical function.
Antiepileptic Drug Use and the Risk of Stroke Among Community‐Dwelling People With Alzheimer Disease: A Matched Cohort Study
Authors: Sarycheva Tatyana , Lavikainen Piia , Taipale Heidi , Tiihonen Jari , Tanskanen Antti , Hartikainen Sirpa , Tolppanen Anna‐Maija
Published: September 2018

Background

People with Alzheimer disease (
AD
) are more predisposed to seizures than older people in general, and use of antiepileptic drugs (
AED
s) is more frequent.
AED
use has been linked to a higher risk of vascular events in the general population; however, it is not evident whether the same risk exists in people with
AD
. We assessed the risk of stroke associated with incident
AED
use among people with
AD
.

Methods and Results

The
MEDALZ
(Medication Use and Alzheimer's Disease) cohort includes all Finnish people who received a clinically verified
AD
diagnosis (N=70718) from 2005 to 2011. People with previous strokes were excluded. For each incident
AED
user (n=5617) one nonuser was matched according to sex, age, and time since
AD
diagnosis. Analyses were conducted with Cox proportional hazards models and inverse probability of treatment weighting. Compared with nonuse,
AED
use was associated with an increased risk of stroke (inverse probability of treatment weighting hazard ratio (
HR
), 1.37; 95% confidence interval [CI], 1.07–1.74). The risk was strongest during the first 90 days (adjusted
HR
, 2.36; 95%
CI
, 1.25–4.47) of
AED
use. According to stroke type, the association was with ischemic strokes (inverse probability of treatment weighting
HR
, 1.34; 95%
CI
, 1.00–1.79) and hemorrhagic ones (inverse probability of treatment weighting
HR
, 1.44; 95%
CI
, 0.86–2.43). The stroke risk of users of older
AED
s did not differ from that of the users of newer
AED
s (adjusted
HR
, 1.04; 95%
CI
, 0.71–1.53).

Conclusions

AED
use was related to an increased risk of stroke, regardless of
AED
type. Our results highlight caution in
AED
use in this vulnerable population.
Renin‐Angiotensin‐Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA
Authors: Joseph Joshua J. , Echouffo Tcheugui Justin B. , Effoe Valery S. , Hsueh Willa A. , Allison Matthew A. , Golden Sherita H.
Published: September 2018

Background

Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross‐sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (
IR
), β‐cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study.

Methods and Results

Homeostatic model assessment of
IR
(
HOMA
2‐
IR
) and
HOMA
2‐β were used to estimate
IR
and β‐cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti‐diabetic medication use at follow‐up. Linear regression was used to examine cross‐sectional associations of aldosterone with fasting plasma glucose,
HOMA
2‐
IR
and
HOMA
2‐β; Cox regression was used to estimate hazard ratios (
HR
) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non‐Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log‐aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher
HOMA
2‐
IR
and 6% higher
HOMA
2‐β (
P
<0.01). A 1‐
SD
increase in log‐aldosterone was associated with a 44% higher risk of incident diabetes mellitus (
P
<0.01) with the greatest increase of 142% (
P
<0.01) observed in Chinese Americans (
P
for interaction=0.09 versus other ethnicities). Similar cross‐sectional findings for log‐plasma renin activity existed, but log‐plasma renin activity was not associated with incident diabetes mellitus after full adjustment.

Conclusions

Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.
Cardiac Surgery Compared With Antibiotics Only in Patients Developing Infective Endocarditis After Transcatheter Aortic Valve Replacement
Authors: Mangner Norman , Leontyev Sergey , Woitek Felix J. , Kiefer Philipp , Haussig Stephan , Binner Christian , Mende Meinhard , Schlotter Florian , Stachel Georg , Höllriegel Robert , Hommel Jennifer , Binner‐Oussenek Katrin , Misfeld Martin , Thiele Holger , Borger Michael A. , Holzhey David , Linke Axel
Published: September 2018

Background

Infective endocarditis (
IE
) after transcatheter aortic valve replacement is a devastating complication associated with a high mortality. Our objective was to determine the impact of cardiac surgery (CS) and antibiotics (
IE
‐
CS
) compared with medical treatment with antibiotics only (
IE
‐
AB
x) on 1‐year mortality in patients developing
IE
after transcatheter aortic valve replacement.

Methods and Results

Patients developing
IE
after transcatheter aortic valve replacement were included in this retrospective analysis. All‐cause 1‐year mortality was the primary end point. A total of 20 patients underwent
IE
‐
CS
compared with 44 patients treated by
IE
‐
AB
x. In this unmatched cohort, patients treated by
IE
‐
AB
x were older (
P
=0.006), had a higher Society of Thoracic Surgeons score (
P
=0.029), and more often had severe chronic kidney disease (
P
=0.037). One‐year mortality was not different between groups (
IE
‐CS versus IE‐ABx, 65% versus 68.2%;
P
=0.802). The rate of any complication during treatment was higher in the
IE
‐
CS
group (
P
=0.024). In a matched cohort, baseline characteristics were not significantly different. All‐cause 1‐year mortality was not different between groups (
IE
‐CS versus IE‐ABx, 65% versus 75%;
P
=0.490). A Cox regression analysis revealed any indication for surgery (hazard ratio, 6.20; 95% confidence interval, 1.80–21.41;
P
=0.004), sepsis on admission (hazard ratio, 4.03; 95% confidence interval, 1.97–8.24;
P
<0.001), and mitral regurgitation ≥2 (hazard ratio, 2.91; 95% confidence interval, 1.33–6.37) as factors associated with 1‐year mortality.

Conclusions

In patients developing
IE
after transcatheter aortic valve replacement, mortality was predicted by the severity of
IE
and concomitant mitral regurgitation. In this small, and therefore statistically limited, but high‐risk patient cohort, CS provided no significant mortality benefit compared with medical therapy. Individual decision making by a “heart and endocarditis team” is necessary to offer those patients the most reasonable treatment option.
(In)direct Reference in the Phonology-Syntax Interface under Phase Theory: A Response to “Modular PIC” (D’Alessandro and Scheer 2015)
Authors: Bonet Eulàlia , Cheng Lisa Lai-Shen , Downing Laura J. , Mascaró Joan
Published: September 2018

Although in many interface theories, the domains of phrasal phonological processes are defined in terms of prosodic constituents, D’Alessandro and Scheer (2015) argue that their proposed modification of phase theory, Modular PIC, renders prosodic constituents superfluous. Phrasal phonological domains can instead be defined directly in the syntax. In this response, we argue that Modular PIC does not provide a convincing new approach to the syntax-phonology interface, as it is both too powerful and too restrictive. We show that the analysis offered of raddoppiamento fonosintattico in Eastern Abruzzese does not justify the loss of restrictiveness Modular PIC brings to phase theory. We also show that Modular PIC is too restrictive to account for phenomena, from Bantu languages and others, that have received satisfactory analyses within interface theories that appeal to prosodic constituents. We conclude that Modular PIC does not successfully replace prosodic constituent approaches to the interface.
The Drama of Infertility: Reading Isa 56:1-8 from a Krobo Perspective
Authors: Gatti Nicoletta , Ossom-Batsa George
Published: September 2018

In most cultures in Ghana, both male and female infertility are believed to be a curse and a sign of an unfruitful life. The ability to procreate thus defines the identity of the person and his/her existential value in relation to others. Furthermore, childlessness becomes an overwhelming drama as it is perceived to depict an inferior state of being or a life of incompleteness. This type of social identity construction raises serious hermeneutical issues in its engagement with the Judeo-Christian message of inclusiveness. Against this backdrop, this study reads the drama surrounding infertility within the Krobo worldview from the horizon of Isa 56:1-8, using the Communicative hermeneutic approach. Our findings are that an engagement between the Krobo worldview and the Isaian text creates both tension and transformation. The tension comes about because of the contrast of views; and the transformation resides in the change of perspective. The text provides a rich and an alternative understanding of infertility: another way of being and not a curse.
Pious Eli? The Characterization of Eli in 1 Samuel 3:18
Authors: Cook Ryan
Published: September 2018

In 1 Sam 3:18b, Eli responds to a prophetic judgment with the phrase “it is the Lord, may he do what is good in his eyes.” Most commentators understand this response as an example of pious acceptance of divine judgment. The claim of this article is that a plausible case can be made for reading Eli’s response as culpably passive. This case will be made following two lines of evidence. First, I will examine an oracle of judgment against an individual and the response as a type-scene in Samuel-Kings. Second, I will examine how this culpable passivity fits with the characterization of Eli in 1 Samuel 1-3.
The Good Shepherd παροιμία (John 10:1-21) and John’s Implied Audience: A Thought Experiment in Reading the Fourth Gospel
Authors: Skinner Christopher William
Published: September 2018

It is often said that the Johannine Jesus never utters a narrative parable like those that are so ubiquitous throughout the Synoptics. However, in John 10, we have the closest parallel in the so-called “Good Shepherd” discourse, where Jesus uses a “figure of speech” (παροιµία) to compare himself to a benevolent or noble shepherd. The present article will explore this παροιµία in light of the unfolding narrative Christology over the first nine chapters. Against that backdrop, we will examine the questions: “What historical information can reasonably be inferred as part of the literary construct known as the implied audience?”, and “How has the implied audience been prepared by the narrator to receive this metaphorical speech?”
Two new species of Amanita (Amanitaceae) from North-western Himalaya, India
Authors: MEHMOOD TAHIR , DAS KANAD , HOSEN MD. IQBAL , BHATT R.P. , UNIYAL PRIYANKA , SINGH UPENDRA
Published: September 2018

Two new species of the genus Amanita are described from India. Amanita argenteoalba, a member of subgenus Lepidella section Lepidella, is characterized by its small to medium sized basidiocarps, white to silvery white pileus with brownish orange tinge, universal veil on pileus as floccose-felted to subfelted patches, rooting bulb covered by recurved scales on its upper parts, subglobose basidiospores, the absence of clamp connections in the basidioma and universal veil on pileus comprising of irregularly arranged inflated cells with scattered to frequent filamentous hyphae and occurrence in broad leaf forest under Rhododendron arboreum. Amanita dhakuriana, a representative member of subgenus Amanita section Vaginatae, is characterized by its small sized basidiocarps, the pileus that is greenish grey over centre and pale grey towards the margin and subglobose to broadly ellipsoid basidiospores. Both species are described, illustrated and compared with morphologically similar taxa, and nrLSU-based phylogenetic analyses were provided.
A new and unusual endemic species from the Chihuahuan Desert, Mexico: Antiphytum geoffreyi (Boraginaceae, Echiochiloideae)
Authors: MENDOZA-DÍAZ NIDIA , FLORES-OLVERA HILDA , SIMPSON MICHAEL G. , MOORE MICHAEL J.
Published: September 2018

A new and unusual species of Antiphytum, here named A. geoffreyi, is described and illustrated. This new species is assigned to the genus Antiphytum because it possesses eremocarps directly attached to a pyramidal gynobase, which forms a ventral cicatrix on the eremocarp. However, it is unique within Antiphytum in having multiple inflorescence branches arising nearly at the base of the plant, a triangular-pyramidal gynobase, and the proportionally longest eremocarp cicatrix of the genus. Some of these characteristics are reminiscent of Ogastemma, the sister genus of Antiphytum, making A. geoffreyi of potential great significance in the systematics of Boraginaceae subfam. Echiochiloideae. Among species of Antiphytum, A. geoffreyi is most similar to A. peninsulare, with which it shares a triangular-shaped eremocarp, but it differs from this species in possessing an infra-medial cicatrix and a smaller corolla limb diameter. The new species is known from only two collections in Coahuila, Mexico, both made by the Hinton family, who have discovered many new species in their extensive explorations of the country and provided important specimens to the country’s flora.
Passiflora intricata, an apetalous new species from the Dominican Republic in Supersection Auriculatae (Passifloraceae)
Authors: MACDOUGAL JOHN M. , OCHOA JORGE , KROSNICK SHAWN E.
Published: September 2018

A new species of Passiflora L. endemic to the Dominican Republic, P. intricata, is described and illustrated from herbarium material and living plants. The flower is unusual in Passiflora by its vestigial androgynophore and tangled thread-like corona. It is placed in subgenus Decaloba supersection Auriculatae s.str. on the basis of its plicate operculum, laminar and petiolar nectaries, grooved seeds, very reduced petals (absent in this new species) and apically attenuate coronal filaments.
A new genus and a new species of Schizomyiina (Diptera: Cecidomyiidae: Asphondyliini) inducing petiole galls on Macaranga bancana (Miq.) in Borneo, Malaysia
Authors: ELSAYED AYMAN KHAMIS , SHIMIZU-KAYA USUN , ITIOKA TAKAO , MELENG PAULUS , YUKAWA JUNICHI , TOKUDA MAKOTO
Published: September 2018

We describe a gall midge Macarangamyia itiokai Elsayed & Tokuda gen. n., sp. n. belonging to the subtribe Schizomyiina (Diptera: Cecidomyiidae: Asphondyliini) inducing petiole galls on Macaranga bancana (Miq.) in Lambir Hills National Park, Borneo, Malaysia. The new genus is distinguishable from all known genera of Schizomyiina by the unique dorsally-placed aedeagus slit, the short, membranous, protrusible ovipositor, with scattered strong setae ventrally and dorsally, and the presence of spiracles on all larval thoracic segments. It is compared and separated from its closely related Oriental genera of Schizomyiina.
Myxobolus bragantinus n. sp. (Cnidaria: Myxosporea) from the gill filaments of the redeye mullet, Mugil rubrioculus (Mugiliformes: Mugilidae), on the eastern Amazon coast
Authors: CARDIM JOYCE , SILVA DIEHGO , HAMOY IGOR , MATOS EDILSON , ABRUNHOSA FERNANDO
Published: September 2018

Mullets (Mugilidae) are economically-important fish exploited extensively by artisanal fisheries on the Amazon coast of Brazil. In the present study, 150 specimens of redeye mullet (Mugil rubrioculus) acquired from the public fish market were examined, and the gill filaments of 90 (60%) were found to be infected with spores of Myxobolus. The mature spores were spherical, with a mean diameter of 6.28±0.33 μm, and had polar capsules of equal size (2.47±0.34 μm in length and 1.58±0.27 μm in width). The 18S rRNA sequence of the parasite was compared with those of other myxosporidian species available in the GenBank database. The morphological and molecular characteristics of the parasite indicate strongly the existence of a new species, denominated Myxobolus bragantinus n. sp., the first case of a new myxosporidian species to be found in this host. [Zoobank: urn:lsid:zoobank.org:act:E00F72E1-9302-423F-BA4E-51C05D0770C8]
The Ozone Water–Land Environmental Transition Study: An Innovative Strategy for Understanding Chesapeake Bay Pollution Events
Authors: Sullivan John T. , Berkoff Timothy , Gronoff Guillaume , Knepp Travis , Pippin Margaret , Allen Danette , Twigg Laurence , Swap Robert , Tzortziou Maria , Thompson Anne M. , Stauffer Ryan M. , Wolfe Glenn M. , Flynn James , Pusede Sally E. , Judd Laura M. , Moore William , Baker Barry D. , Al-Saadi Jay , McGee Thomas J.
Published: September 2018

Coastal regions have historically represented a significant challenge for air quality investigations because of water–land boundary transition characteristics and a paucity of measurements available over water. Prior studies have identified the formation of high levels of ozone over water bodies, such as the Chesapeake Bay, that can potentially recirculate back over land to significantly impact populated areas. Earth-observing satellites and forecast models face challenges in capturing the coastal transition zone where small-scale meteorological dynamics are complex and large changes in pollutants can occur on very short spatial and temporal scales. An observation strategy is presented to synchronously measure pollutants “over land” and “over water” to provide a more complete picture of chemical gradients across coastal boundaries for both the needs of state and local environmental management and new remote sensing platforms. Intensive vertical profile information from ozone lidar systems and ozonesondes, obtained at two main sites, one over land and the other over water, are complemented by remote sensing and in situ observations of air quality from ground-based, airborne (both personned and unpersonned), and shipborne platforms. These observations, coupled with reliable chemical transport simulations, such as the National Oceanic and Atmospheric Administration (NOAA) National Air Quality Forecast Capability (NAQFC), are expected to lead to a more fully characterized and complete land–water interaction observing system that can be used to assess future geostationary air quality instruments, such as the National Aeronautics and Space Administration (NASA) Tropospheric Emissions: Monitoring of Pollution (TEMPO), and current low-Earth-orbiting satellites, such as the European Space Agency’s Sentinel-5 Precursor (S5-P) with its Tropospheric Monitoring Instrument (TROPOMI).
The Role of Stochastic Forcing in Generating ENSO Diversity
Authors: Thomas Erin E. , Vimont Daniel J. , Newman Matthew , Penland Cécile , Martínez-Villalobos Cristian
Published: September 2018

Numerous oceanic and atmospheric phenomena influence El Niño–Southern Oscillation (ENSO) variability, complicating both prediction and analysis of the mechanisms responsible for generating ENSO diversity. Predictability of ENSO events depends on the characteristics of both the forecast initial conditions and the stochastic forcing that occurs subsequent to forecast initialization. Within a linear inverse model framework, stochastic forcing reduces ENSO predictability when it excites unpredictable growth or interference after the forecast is initialized, but also enhances ENSO predictability when it excites optimal initial conditions that maximize deterministic ENSO growth. Linear inverse modeling (LIM) allows for straightforward separation between predictable signal and unpredictable noise and so can diagnose its own skill. While previous LIM studies of ENSO focused on deterministic dynamics, here we explore how noise forcing influences ENSO diversity and predictability. This study identifies stochastic forcing details potentially contributing to the development of central Pacific (CP) or eastern Pacific (EP) ENSO characteristics. The technique is then used to diagnose the relative roles of initial conditions and noise forcing throughout the evolution of several ENSO events. LIM results show varying roles of noise forcing for any given event, highlighting its utility in separating deterministic from noise-forced contributions to the evolution of individual ENSO events. For example, the strong 1982 event was considerably more influenced by noise forcing late in its evolution than the strong 1997 event, which was more predictable with long lead times due to its deterministic growth. Furthermore, the 2014 deterministic trajectory suggests that a strong event in 2014 was unlikely.
Relationship Between Postoperative Neutrophil–Lymphocyte Ratio and 6-Month Primary Patency of Percutaneous Transluminal Angioplasty in Femoropopliteal disease With Drug-Coated and Uncoated Balloons
Authors: Zhen Yanhua , Chang Zhihui , Liu Zhaoyu , Zheng Jiahe
Published: September 2018

We investigated the relationship of postoperative neutrophil–lymphocyte ratio (NLR) with 6-month primary patency of percutaneous transluminal angioplasty (PTA) in femoropopliteal disease using drug-coated balloon (DCB) or uncoated balloon (UCB). This retrospective study included 106 patients who received DCB (n = 44) or UCB (n = 62). The postoperative NLR was lower in the DCB group than that in the UCB group (2.60 vs 3.23; P = .004), and 6-month primary patency rate was significantly higher in DCB group than that in the UCB group (77.3% vs 53.2%; P = .011). Multivariate logistic analysis showed that the postoperative NLR was an independent predictor of 6-month primary patency after PTA in patients with femoropopliteal disease (odds ratio: 1.589, 95% confidence interval: 1.078-2.343; P = .019). The cutoff value of postoperative NLR was 3.05 for prediction of 6-month primary patency, with a sensitivity of 64.1% and specificity of 65.7%. The 6-month primary patency rate in the NLR ≤3.05 group was higher than that in the NLR >3.05 group (75.9% vs 47.9%; P = .003). In conclusion, DCB may improve early primary patency by inhibiting inflammation. A higher postoperative NLR was associated with early restenosis.
Subjective Memory Problems and Availability of Emotional Support
Authors: Ha Jung-Hwa , Pai Manacy
Published: September 2018

This study examines (1) whether subjective memory problems (SMP) influence perceived emotional support from and frequency of contact with family and friends; and, (2) the extent to which this relationship is moderated by gender, education, and functional limitations. We use the 2014 wave of the Health and Retirement Study, a nationally representative panel survey of adults aged 51 and over in the United States. While SMP does not affect perceived emotional support for younger group (YG; aged 51–64), in older group (OG; aged 65+), SMP is associated with reduced perceived support from friends. Also, SMP is predictive of fewer writing-based contact with children and friends among OG but not among YG. Lastly, we find that the effect of SMP on support from children is contingent upon activity of daily living (YG) and gender (OG), while the effect of SMP on writing-based contact with both children and friends is contingent upon education (YG only).
In Situ Hybridization for Localization of Ovine Herpesvirus 2, the Agent of Sheep-Associated Malignant Catarrhal Fever, in Formalin-Fixed Tissues
Authors: Pesavento Patricia A. , Cunha Cristina W. , Li Hong , Jackson Kenneth , O’Toole Donal
Published: September 2018

A constraint on understanding the pathogenesis of malignant catarrhal fever (MCF) is the limited number of tools to localize infected cells. The amount of detectable virus, visualized in the past either by immunohistochemistry or in situ hybridization (ISH), has been modest in fixed or frozen tissues. This complicates our understanding of the widespread lymphoid proliferation, epithelial necrosis/apoptosis, and arteritis-phlebitis that characterize MCF. In this work, we developed a probe-based in situ hybridization assay targeting 2 ovine herpesvirus 2 (OvHV-2) genes, as well as their respective transcripts, in formalin-fixed tissues. Using this approach, OvHV-2 nucleic acids were detected in lymphocytes in MCF-affected animals following both natural infection (American bison and domestic cattle) and experimental infection (American bison, rabbits, and pigs). The probe did not cross-react with 4 closely related gammaherpesviruses that also cause MCF: alcelaphine herpesvirus 1, alcelaphine herpesvirus 2, caprine herpesvirus 2, and ibex–MCF virus (MCFV). No signal was detected in control tissues negative for OvHV-2. ISH will be of value in analyzing the natural progression of OvHV-2 infection in time-course studies following experimental infection and in addressing the pathogenesis of MCF.
Valorization of agro-industrial wastes to produce hydrolytic enzymes by fungal solid-state fermentation
Authors: Marzo C. , Díaz A.B. , Caro I. , Blandino A.
Published: September 2018

Nowadays, significant amounts of agro-industrial wastes are discarded by industries; however, they represent interesting raw materials for the production of high-added value products. In this regard, orange peels (ORA) and exhausted sugar beet cossettes (ESBC) have turned out to be promising raw materials for hydrolytic enzymes production by solid state fermentation (SSF) and also a source of sugars which could be fermented to different high-added value products. The maximum activities of xylanase and exo-polygalacturonase (exo-PG) measured in the enzymatic extracts obtained after the SSF of ORA were 31,000 U·kg-1 and 17,600 U·kg-1, respectively; while for ESBC the maximum values reached were 35,000 U·kg-1 and 28,000 U·kg-1, respectively. The enzymatic extracts obtained in the SSF experiments were also employed for the hydrolysis of ORA and ESBC. Furthermore, it was found that extracts obtained from SSF of ORA, supplemented with commercial cellulase, were more efficient for the hydrolysis of ORA and ESBC than a commercial enzyme cocktail typically used for this purpose. In this case, maximum reducing sugars concentrations of 57 and 47 g·L-1 were measured after the enzymatic hydrolysis of ESBC and ORA, respectively.
Tolerance of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) Inhibitors in Patients With Self-Reported Statin Intolerance
Authors: Davidson Erica R. , Snider Melissa J. , Bartsch Kelly , Hirsch Andrea , Li Junan , Larry John
Published: September 2018

Background:

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to lower atherogenic lipid markers in patients with statin intolerance; however, external validity of these findings is unclear in patients with self-reported statin intolerance.

Objective:

The objective of this study was to describe the tolerability of evolocumab and alirocumab in patients with self-reported statin intolerance. Secondary objectives were to describe their efficacy and obtainability.

Methods:

A retrospective chart review was completed and included adult patients with self-reported statin intolerance who were prescribed a PCSK9 inhibitor. Patient-reported side effects, laboratory values, and insurance information were collected for assessment of study objectives.

Results:

During the study period, 55 patients were prescribed PCSK9 inhibitor, 42 started therapy, and 34 had at least 1 follow-up visit. While myalgias occurred in 14.7% (n = 5) of patients, flu-like symptoms in 11.8% (n = 4), and fatigue in 2.9% (n = 1), only 5.9% (n = 2) of prescriptions for PCSK9 inhibitors were discontinued. Low-density lipoprotein cholesterol (LDL-C) was reduced 48.7% (95% confidence interval [CI]: -1.7%-99.1%), and 20 (58.8%) patients achieved a ≥50% reduction in LDL-C. Regarding obtainability, of the 57 prescriptions written, 77.2% (n = 44) required prior authorization and 5.3% (n = 3) were denied by insurance.

Conclusion:

PCSK9 inhibitors were well tolerated in patients with self-reported statin intolerance.
Paucity of Interlobular Bile Ducts in Multidrug-Resistant P-Glycoprotein 3 (MDR3) Deficiency
Authors: Vij Mukul , Valamparampil Joseph , Shanmugum Naresh , Reddy Srinivas Mettu , Rajindrajith Shaman , Rela Mohamed
Published: September 2018

Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the translocation of phosphatidylcholine across the canalicular membrane of the hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood with progressive cholestasis evolving to cirrhosis and liver failure, requiring liver transplantation. In this article, we report 2 pediatric cases of severe MDR3 deficiency with paucity of interlobular bile ducts. Both underwent living donor liver transplantation at our center for decompensated liver disease and portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with negative MDR3 immunostaining in the explanted liver. Genetic studies revealed homozygous deletion single base pair deletion in exon 24 of the ABCB4 gene in the second child. The patients are on regular follow-up after liver transplant and are doing well. Our report highlights that cholangiopathy in MDR3 deficiency can lead to ductopenia in pediatric livers.
“Playing the system”: Structural factors potentiating mental health stigma, challenging awareness, and creating barriers to care for Canadian public safety personnel
Authors: Ricciardelli Rosemary , Carleton R Nicholas , Mooney Taylor , Cramm Heidi
Published: September 2018

There are growing concerns about the impact of public safety work on the mental health of public safety personnel; as such, we explored systemic and individual factors that might dissuade public safety personnel from seeking care. Public safety personnel barriers to care-seeking include the stigma associated with mental disorders and frequent reports of insufficient access to care. To better understand barriers to care-seeking, we thematically analyzed the optional open-ended final comments provided by over 828 Canadian public safety personnel as part of a larger online survey designed to assess the prevalence of mental disorders among public safety personnel. Our results indicated that systematic processes may have (1) shaped public safety personnel decisions for care-seeking, (2) influenced how care-seekers were viewed by their colleagues, and (3) encouraged under-awareness of personal mental health needs. We described how public safety personnel who do seek care may be viewed by others; in particular, we identified widespread participant suspicion that coworkers who took the time to address their mental health needs were “abusing the system.” We explored what constitutes “abusing the system” and how organizational structures—systematic processes within different public safety organizations—might facilitate such notions of abuse. We found that understaffing may increase scrutiny of injured public safety personnel by those left to manage the additional burden; in addition, cynicism and unacknowledged structural stigma may emerge, preventing the other public safety personnel from identifying their mental health needs and seeking help. Finally, we discuss how system-level stigma can be potentiated by fiscal constraints when public safety personnel take any leave of absence, inadvertently contributing to an organizational culture wherein help-seeking for employment-related mental health concerns becomes unacceptable. Implications for public safety personnel training and future research needs are discussed.
Evaluation of the smoking intervention X:IT after the second year: A randomized controlled trial
Authors: Andersen Anette , Bast Lotus S. , Due Pernille , Thygesen Lau C.
Published: September 2018

Aims:Review studies on the long-term effects of school-based smoking interventions show mixed results. X:IT was a three-year cluster randomized controlled trial to prevent uptake of smoking among Danish students from age 13 years until age 15 years which previously proved effective in preventing smoking after the first year of intervention. The aim of this paper was to conduct the pre-planned analyses of the effects of the X:IT intervention on smoking after the second year. Methods: We used self-reported questionnaire data from students at baseline, first, second, and third follow-up ( n at second follow-up=3269, response rate=79.4%). Data from third follow-up were not suitable for analysis. Outcome measure: ‘current smoking’, dichotomised into smoke daily, weekly, monthly or more seldom versus do not smoke. We performed multilevel, logistic regression analyses of available cases and intention-to-treat (ITT) analyses, replacing missing outcome values by multiple imputation. Results: The prevalence of smoking increased from 5.8% at baseline to 17.0% at second follow-up among students at intervention schools, and from 7.6% to 18.7% among students at control schools. Analyses of available cases and ITT analyses did not support X:IT being effective in preventing smoking after the second year of intervention. Conclusions: Although X:IT was effective after the first year of intervention, we were not able to demonstrate any effects after the second year. Implementation of the intervention was lower in the second year compared to the first year which indicates that the missing effect of the intervention at second follow-up is due to lack of implementation.