bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative hematoma with subcutaneous ICD implantation: Impact of anticoagulation and antiplatelet therapies
Authors: Sheldon Seth H. , Cunnane Ryan , Lavu Madhav , Parikh Valay , Atkins Donita , Reddy Yeruva Madhu , Berenbom Loren D. , Emert Martin P. , Pimentel Rhea , Dendi Raghuveer , Lakkireddy Dhanunjaya R. 
Published: April 2018

AbstractBackgroundThe safety of perioperative anticoagulation (AC) and antiplatelet (AP) therapy with subcutaneous implantable cardioverter‐defibrillator (S‐ICD) implantation is unknown. The purpose of this study was to identify the risk factors associated with hematoma complicating S‐ICD implantation.MethodsRecords were retrospectively reviewed from 200 consecutive patients undergoing S‐ICD implantation at two academic medical centers. A hematoma was defined as a device site blood accumulation requiring surgical evacuation, extended hospital stay, or transfusion.ResultsAmong 200 patients undergoing S‐ICD implantation (age 49 ± 17 years, 67% men), 10 patients (5%) had a hematoma, which required evacuation in six patients (3%). Warfarin was bridged or uninterrupted in 12 and 13 patients, respectively (6% and 6.5%). Four of 12 patients with warfarin and bridging AC (33%) and two of 13 patients with uninterrupted warfarin (15%) developed a hematoma. Neither of the two patients with uninterrupted DOAC had a hematoma. No patients on interrupted AC without bridging (n = 26, 13 with warfarin, 13 with DOAC) developed a hematoma. A hematoma was also more likely with the use of clopidogrel (n = 4/10 vs 10/190, 40% vs 5.3%, P < 0.0001) in combination with aspirin in 12/14 patients. Any bridging AC (odds ratio [OR] 10.3, 1.8–60.8, P = 0.01), clopidogrel (OR 10.0, 1.7–57.7, P = 0.01), and uninterrupted warfarin without bridging (OR 11.1, 1.7–74.3, P = 0.013) were independently associated with hematoma formation.ConclusionAC and/or AP therapy with clopidogrel appears to increase the risk for hematoma following S‐ICD implantation. Interruption of AC without bridging should be considered when it is an acceptable risk to hold AC.
Use of digoxin in atrial fibrillation: One step further in the mortality controversy from the AFFIRM study
Authors: Charnigo Richard , Khairy Paul , Guo Jing , Shohoudi Azadeh , Elayi Claude S. 
Published: April 2018

AbstractBackgroundWhether there is a causal association between digoxin and mortality among patients with atrial fibrillation (AF), with or without congestive heart failure (HF), has been controversial; in particular, two prior analyses of data from the Atrial Fibrillation Follow‐up Investigation of Rhythm Management (AFFIRM) trial have yielded conflicting results. We sought to investigate how digoxin impacts mortality, in the full AFFIRM cohort and for various subgroups, by applying marginal structural modeling (MSM) to AFFIRM data.MethodsMSM is a newer statistical approach, which estimates causal association in the absence of randomization. MSM more effectively accounts for time‐varying treatment and mitigates potential biases, in contrast to the two statistical approaches used in prior analyses of the AFFIRM data.ResultsAmong 4,060 patients in AFFIRM, 660 (16.3%) died during follow‐up. Digoxin was associated with significantly higher mortality in the full cohort (estimated hazard ratio [HR] 1.33, 95% confidence interval [CI] 1.11–1.60, P = 0.002) and in 3,121 patients without HF (HR 1.36, 95% CI 1.07–1.72, P = 0.011). There was a trend toward higher mortality with digoxin in 939 patients with HF (HR 1.29, 95% CI 0.96–1.72, P = 0.090). Associations were nonsignificant in 463 patients with HF and left ventricular ejection fraction (EF) ≥40% and in 155 patients with EF ≤30%.ConclusionsDigoxin is associated with significantly increased mortality among AFFIRM patients collectively, as determined by MSM statistical methodology. However, the impact of digoxin among AFFIRM patients with coexisting HF is inconclusive.
The impact of oral food challenges for food allergy on quality of life: A systematic review
Authors: Kansen Hannah M. , Le Thuy‐My , Meijer Yolanda , Flokstra‐de Blok Bertine M. J. , Welsing Paco M. J. , van der Ent Cornelis K. , Knulst André C. , van Erp Francine C. 
Published: April 2018

AbstractBackgroundFood allergy significantly impairs health‐related quality of life (HRQL). Currently, it is still unknown whether diagnostic interventions for food allergy improve HRQL. We aim to assess the impact of diagnostic interventions for food allergy on HRQL.MethodsA systematic search was performed in MEDLINE, Embase, Cochrane Library, and CINAHL focused on patients with a (suspected) food allergy who underwent diagnostic interventions (ie, skin prick test, specific IgE, or oral food challenges [OFC]) and in whom HRQL was assessed. The mean difference between HRQL before and after the diagnostic intervention was calculated. A minimal clinically important difference of 0.5 was considered clinically relevant for the food allergy quality of life questionnaire.ResultsSeven of 1465 original identified publications were included in which the impact of an OFC on HRQL was investigated (total patients n = 1370). No other diagnostic interventions were investigated. Food allergy‐specific parent‐reported HRQL improved significantly after an OFC irrespective of the outcome in children with a suspected food allergy in two publications. The change was considered clinically relevant in one of two publications. In addition, parent‐reported HRQL improved after an OFC to assess the eliciting dose in children with a confirmed food allergy. The parental burden was significantly reduced after an OFC to assess resolution of food allergy. A meta‐analysis could not be performed due to the limited numbers of, and considerable heterogeneity between, eligible publications.ConclusionAn OFC is associated with an improved food allergy‐specific HRQL and a reduced parental burden of food allergy.
Constructing Treatment Decision Rules Based on Scalar and Functional Predictors when Moderators of Treatment Effect are Unknown
Authors: Ciarleglio Adam , Petkova Eva , Ogden Todd , Tarpey Thaddeus 
Published: April 2018

SummaryTreatment response heterogeneity poses serious challenges for selecting treatment for many diseases. To understand this heterogeneity better and to help in determining the best patient-specific treatments for a given disease, many clinical trials are collecting large amounts of patient level data before administering treatment in the hope that some of these data can be used to identify moderators of treatment effect. These data can range from simple scalar values to complex functional data such as curves or images. Combining these various types of baseline data to discover ‘biosignatures’ of treatment response is crucial for advancing precision medicine. Motivated by the problem of selecting optimal treatment for subjects with depression based on clinical and neuroimaging data, we present an approach that both identifies covariates associated with differential treatment effect and estimates a treatment decision rule based on these covariates. We focus on settings where there is a potentially large collection of candidate biomarkers consisting of both scalar and functional data. The validity of the approach proposed is justified via extensive simulation experiments and illustrated by using data from a placebo-controlled clinical trial investigating antidepressant treatment response in subjects with depression.
Spatially Balanced Sampling of Continuous Populations
Authors: Grafström Anton , Matei Alina 
Published: April 2018

AbstractWhen sampling from a continuous population (or distribution), we often want a rather small sample due to some cost attached to processing the sample or to collecting information in the field. Moreover, a probability sample that allows for design‐based statistical inference is often desired. Given these requirements, we want to reduce the sampling variance of the Horvitz–Thompson estimator as much as possible. To achieve this, we introduce different approaches to using the local pivotal method for selecting well‐spread samples from multidimensional continuous populations. The results of a simulation study clearly indicate that we succeed in selecting spatially balanced samples and improve the efficiency of the Horvitz–Thompson estimator.
Patient blood management and the importance of the Transfusion Practitioner role to embed this into practice
Authors: Bielby L. , Moss R. L. 
Published: April 2018

SUMMARYPatient blood management (PBM) is a widely established international initiative, with a multidisciplinary approach to reduce transfusion. The Transfusion Practitioner1 (TP) role is well embedded in the United Kingdom (UK) and Australia. The value of the TP in changing both culture and practice to implement an all‐inclusive PBM approach to care will be discussed. The TP role was born from both a safety and haemovigilance culture, where the greatest identified risk to the patient undergoing a transfusion was human error. From this initial trigger for improved safety, the TP role has evolved to a multifaceted, highly specialised role, involved in both PBM and transfusion processes. As the transfusion paradigm shifted from product to patient, the TP role evolved to include PBM, with an emphasis on the patients and the impact transfusion has on them. A multidisciplinary team is required to drive both PBM and transfusion; the TP is recognised as a critical link in the multidisciplinary team. They are seen as a driving force for change, bridging the gap between the laboratory and clinical arenas. The TP plays a vital role in helping establish and embed PBM that improves patient and safety outcomes.
Patient blood management: how is implementation going?: A report comparing the 2015 survey with the 2013 survey of PBM in England
Authors: Sherliker L. , Pendry K. , Hockley B. 
Published: April 2018

SUMMARYBackgroundPatient blood management (PBM) is an evidence‐based approach to optimising the care of patients who might need transfusion. In 2013, all NHS Trusts in England were surveyed about their readiness to implement PBM. National PBM recommendations were launched in 2014.AimsThe aim of this study was to determine progress of PBM initiatives.Methods/MaterialsA survey was constructed by staff in hospitals and NHS Blood and Transplant (NHSBT). An online questionnaire was sent to all NHS Trusts in England (N = 149) in November 2015.ResultsImprovements in 2015:
Education/training in transfusion: 80–100% from 60–90% in 2013
Provision of information relating to consent for transfusion: 98% from 65% in 2013 (P = <0·001)
The management of anaemia: elective general surgery management, 66% from 41% in 2013 (P = <0·001)

Transfusion alternatives: Tranexamic use in surgery, 92% from 71% in 2013 (P = <0·001)

Laboratory staff empowered to challenge transfusion requests, 95% from 65% in 2013 (P = 0·001)

Further work required:
Electronic systems to support requesting (e.g. mandatory recording of diagnosis: 47% from 48% in 2013 (P = 0·85), incorporation of standardised requesting codes: 27% from 33% in 2013 (P = 0·24)
Appropriate use of components: in 2015, only 42% had a lower red cell transfusion thresholds policy in non‐bleeding patients

ConclusionsThe results provided information to support the development of local and national work plans. It is hoped that the collaborative work across NHS Blood and Transplant (NHSBT), the National Blood Transfusion Committee (NBTC) and NHS Trusts will continue to drive the PBM agenda to support best practice in this field.
Interaction of maternal environment and allelic differences in seed vigour genes determines seed performance in Brassica oleracea
Authors: Awan Sajjad , Footitt Steven , Finch‐Savage William E. 
Published: April 2018

SummarySeed vigour is a key trait essential for the production of sustainable and profitable crops. The genetic basis of variation in seed vigour has recently been determined in Brassica oleracea, but the relative importance of the interaction with parental environment is unknown. We produced seeds under a range of maternal environments, including global warming scenarios. Lines were compared that had the same genetic background, but different alleles (for high and low vigour) at the quantitative trait loci responsible for determining seed vigour by altering abscisic acid (ABA) content and sensitivity. We found a consistent effect of beneficial alleles across production environments; however, environmental stress during production also had a large impact that enhanced the genetic difference in seed performance, measured as germination speed, resistance to controlled deterioration and induction of secondary dormancy. Environmental interaction with allelic differences in key genes that determine ABA content and sensitivity develops a continuity in performance from rapid germination through to failure to complete germination, and increasing depths of seed dormancy. The genetic–environmental interaction revealed provides a robust mechanism of bet‐hedging to minimize environmental risk during subsequent germination, and this could have facilitated the rapid change in seed behaviour (reduced dormancy and rapid germination) observed during crop domestication.
A working model for hypothermic neuroprotection
Authors: Wassink Guido , Davidson Joanne O. , Lear Christopher A. , Juul Sandra E. , Northington Frances , Bennet Laura , Gunn Alistair J. 
Published: April 2018

AbstractTherapeutic hypothermia significantly improves survival without disability in near‐term and full‐term newborns with moderate to severe hypoxic–ischaemic encephalopathy. However, hypothermic neuroprotection is incomplete. The challenge now is to find ways to further improve outcomes. One major limitation to progress is that the specific mechanisms of hypothermia are only partly understood. Evidence supports the concept that therapeutic cooling suppresses multiple extracellular death signals, including intracellular pathways of apoptotic and necrotic cell death and inappropriate microglial activation. Thus, the optimal depth of induced hypothermia is that which effectively suppresses the cell death pathways after hypoxia–ischaemia, but without inhibiting recovery of the cellular environment. Thus mild hypothermia needs to be continued until the cell environment has recovered until it can actively support cell survival. This review highlights that key survival cues likely include the inter‐related restoration of neuronal activity and growth factor release. This working model suggests that interventions that target overlapping mechanisms, such as anticonvulsants, are unlikely to materially augment hypothermic neuroprotection. We suggest that further improvements are most likely to be achieved with late interventions that maximise restoration of the normal cell environment after therapeutic hypothermia, such as recombinant human erythropoietin or stem cell therapy.
image
Synaptic depression induced by postsynaptic cAMP production in the Drosophila mushroom body calyx
Authors: Sato Shoma , Ueno Kohei , Saitoe Minoru , Sakai Takaomi 
Published: April 2018

Key points
Synaptic potentiation in Drosophila is observed at cholinergic synapses between antennal lobe (AL) and mushroom body (MB) neurons in the adult brain; however, depression at the AL–MB synapses has not yet been identified.
By ex vivo Ca2+ imaging in an isolated cultured Drosophila brain, we found novel activity‐dependent depression at the AL–MB synapses.
The degree of Ca2+ responses after repetitive AL stimulation is significantly reduced in the dendritic region of MB neurons (calyx) compared with those before AL stimulation, and this reduction of Ca2+ responses remains for at least 30 min.
The expression of rutabaga, which encodes Ca2+/calmodulin‐dependent adenylyl cyclase, is essential in the MB neurons for the reduction of Ca2+ responses in the calyx.
Our study reveals that elevation of cAMP production in the calyx during repetitive AL stimulation induces the depression at the AL–MB synapses.
AbstractSynaptic plasticity has been studied to reveal the molecular and cellular mechanisms of associative and non‐associative learning. The fruit fly Drosophila melanogaster can be used to identify the molecular mechanisms of synaptic plasticity because vast genetic information or tools are available. Here, by ex vivo Ca2+ imaging of an isolated cultured Drosophila brain, we examined the novel activity‐dependent synaptic depression between the projection neurons of the antennal lobe (AL) and mushroom body (MB). Ex vivo Ca2+ imaging analysis revealed that electrical stimulation of AL elicits Ca2+ responses in the dendritic (calyx) and axonal (α lobe) regions of MB neurons, and the responses are reduced after repetitive AL stimulation. Since the cAMP signalling pathway plays an important role in synaptic plasticity in invertebrates and vertebrates, we examined whether the reduction of Ca2+ responses is also regulated by the cAMP signalling pathway. The expression of rutabaga (rut), which encodes Ca2+/calmodulin‐dependent adenylyl cyclase, was essential for the reduction of Ca2+ responses in the calyx and α lobe. Furthermore, imaging analysis using a fluorescence resonance energy transfer‐based cAMP indicator revealed that the cAMP level increased in the wild‐type calyx during repetitive AL stimulation, whereas it decreased in rut1mutant flies with a loss‐of‐function mutation of rut. Thus, our study suggests that an increase in postsynaptic cAMP level during repetitive AL stimulation contributes to the attenuation of inputs at AL–MB synapses.
Redefinition and Unification of the SXT/R391 Family of Integrative and Conjugative Elements
Authors: Bioteau Audrey , Durand Romain , Burrus Vincent 
Published: April 2018

ABSTRACTIntegrative and conjugative elements (ICEs) of the SXT/R391 family are key drivers of the spread of antibiotic resistance inVibrio cholerae, the infectious agent of cholera, and other pathogenic bacteria. The SXT/R391 family of ICEs was defined based on the conservation of a core set of 52 genes and site-specific integration into the 5′ end of the chromosomal geneprfC. Hence, the integrase geneinthas been intensively used as a marker to detect SXT/R391 ICEs in clinical isolates. ICEs sharing most core genes but differing by their integration site and integrase gene have been recently reported and excluded from the SXT/R391 family. Here we explored the prevalence and diversity of atypical ICEs in GenBank databases and their relationship with typical SXT/R391 ICEs. We found atypical ICEs inV. choleraeisolates that predate the emergence and expansion of typical SXT/R391 ICEs in the mid-1980s in seventh-pandemic toxigenicV. choleraestrains O1 and O139. Our analyses revealed that while atypical ICEs are not associated with antibiotic resistance genes, they often carry cation efflux pumps, suggesting heavy metal resistance. Atypical ICEs constitute a polyphyletic group likely because of occasional recombination events with typical ICEs. Furthermore, we show that the alternative integration and excision genes of atypical ICEs remain under the control of SetCD, the main activator of the conjugative functions of SXT/R391 ICEs. Together, these observations indicate that substitution of the integration/excision module and change of specificity of integration do not preclude atypical ICEs from inclusion into the SXT/R391 family.IMPORTANCEVibrio choleraeis the causative agent of cholera, an acute intestinal infection that remains to this day a world public health threat. Integrative and conjugative elements (ICEs) of the SXT/R391 family have played a major role in spreading antimicrobial resistance in seventh-pandemicV. choleraebut also in several species ofEnterobacteriaceae. Most epidemiological surveys use the integrase gene as a marker to screen for SXT/R391 ICEs in clinical or environmental strains. With the recent reports of closely related elements that carry an alternative integrase gene, it became urgent to investigate whether ICEs that have been left out of the family are a liability for the accuracy of such screenings. In this study, based on comparative genomics, we broaden the SXT/R391 family of ICEs to include atypical ICEs that are often associated with heavy metal resistance.
Biofilms Comprise a Component of the Annual Cycle of Vibrio cholerae in the Bay of Bengal Estuary
Authors: Sultana Marzia , Nusrin Suraia , Hasan Nur A. , Sadique Abdus , Ahmed Kabir U. , Islam Atiqul , Hossain Anwar , Longini Ira , Nizam Azhar , Huq Anwar , Siddique Abul K. , Sack David A. , Sack Richard B. , Colwell Rita R. , Alam Munirul 
Published: April 2018

ABSTRACT

Vibrio cholerae
, an estuarine bacterium, is the causative agent of cholera, a severe diarrheal disease that demonstrates seasonal incidence in Bangladesh. In an extensive study of
V. cholerae
occurrence in a natural aquatic environment, water and plankton samples were collected biweekly between December 2005 and November 2006 from Mathbaria, an estuarine village of Bangladesh near the mangrove forests of the Sundarbans. Toxigenic
V. cholerae
exhibited two seasonal growth peaks, one in spring (March to May) and another in autumn (September to November), corresponding to the two annual seasonal outbreaks of cholera in this region. The total numbers of bacteria determined by heterotrophic plate count (HPC), representing culturable bacteria, accounted for 1% to 2.7% of the total numbers obtained using acridine orange direct counting (AODC). The highest bacterial culture counts, including toxigenic
V. cholerae
, were recorded in the spring. The direct fluorescent antibody (DFA) assay was used to detect
V. cholerae
O1 cells throughout the year, as free-living cells, within clusters, or in association with plankton.
V. cholerae
O1 varied significantly in morphology, appearing as distinctly rod-shaped cells in the spring months, while small coccoid cells within thick clusters of biofilm were observed during interepidemic periods of the year, notably during the winter months. Toxigenic
V. cholerae
O1 was culturable in natural water during the spring when the temperature rose sharply. The results of this study confirmed biofilms to be a means of persistence for bacteria and an integral component of the annual life cycle of toxigenic
V. cholerae
in the estuarine environment of Bangladesh.

IMPORTANCE
Vibrio cholerae
, the causative agent of cholera, is autochthonous in the estuarine aquatic environment. This study describes morphological changes in naturally occurring
V. cholerae
O1 in the estuarine environment of Mathbaria, where the bacterium is culturable when the water temperature rises and is observable predominantly as distinct rods and dividing cells. In the spring and fall, these morphological changes coincide with the two seasonal peaks of endemic cholera in Bangladesh.
V. cholerae
O1 cells are predominantly coccoid within biofilms but are rod shaped as free-living cells and when attached to plankton or to particulate matter in interepidemic periods of the year. It is concluded that biofilms represent a stage of the annual life cycle of
V. cholerae
O1, the causative agent of cholera in Bangladesh.