bluuebunny/crossref_metadata_2025_split huggingface dataset:
Approximate controllability of impulsive fractional integro-differential equation with state-dependent delay in Hilbert spaces
Authors: Zhou Yong , Suganya S , Arjunan M Mallika , Ahmad B 
Published: December 2017

Abstract
In this paper, the problem of approximate controllability for non-linear impulsive fractional integro-differential equation with state-dependent delay in Hilbert spaces is investigated. We study the approximate controllability for non-linear impulsive integro-differential systems under the assumption that the corresponding linear control system is approximately controllable. By utilizing the methods of fractional calculus, semigroup theory, fixed-point theorem coupled with solution operator, sufficient conditions are formulated and proved. Finally, an example is provided to illustrate the proposed theory.
Lagrangian Constant Cycle Subvarieties in Lagrangian Fibrations
Authors: Lin Hsueh-Yung 
Published: December 2017

Abstract
We show that the image of a dominant meromorphic map from an irreducible compact Calabi–Yau manifold X whose general fiber is of dimension strictly between 0 and $\dim X$ is rationally connected. Using this result, we construct for any hyper-Kähler manifold X admitting a Lagrangian fibration a Lagrangian constant cycle subvariety ΣH in X which depends on a divisor class H whose restriction to some smooth Lagrangian fiber is ample. If $\dim X = 4$, we also show that up to a scalar multiple, the class of a zero-cycle supported on ΣH in CH0(X) depend neither on H nor on the Lagrangian fibration (provided b2(X) ≥ 8).
Early Identification of Acute Respiratory Distress Syndrome in the Absence of Positive Pressure Ventilation: Implications for Revision of the Berlin Criteria for Acute Respiratory Distress Syndrome
Authors: Coudroy Rémi , Frat Jean-Pierre , Boissier Florence , Contou Damien , Robert René , Thille Arnaud W. 
Published: December 2017

Objectives:
To assess whether patients breathing spontaneously under standard oxygen could be recognized early as acute respiratory distress syndrome patients according to the current Berlin definition.

Design:
A post hoc analysis from two prospective studies.

Setting:
Twenty-three French ICUs.

Patients:
All patients admitted for acute hypoxemic respiratory failure and treated with noninvasive ventilation were analyzed. Patients with cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease, or hypercapnia were excluded.

Interventions:
None.

Measurements and Main Results:
The Pao
2/Fio
2 ratio was estimated at admission under standard oxygen and then under noninvasive ventilation 1 hour after initiation and within the first 24 hours. Among the 219 patients treated with noninvasive ventilation for acute hypoxemic respiratory failure, 180 (82%) had bilateral infiltrates including 161 patients with Pao
2/Fio
2 less than or equal to 300 mm Hg under standard oxygen. Among them, 127 were treated with positive end-expiratory pressure of at least 5 cm H2O, and 120 (94%) fulfilled criteria for acute respiratory distress syndrome within the first 24 hours. The mortality rate of patients with bilateral infiltrates and Pao
2/Fio
2 less than or equal to 300 mm Hg under standard oxygen was 29%, a rate very close to that of intubated patients with acute respiratory distress syndrome in the Berlin definition.

Conclusions:
Almost all patients with pulmonary bilateral infiltrates and a Pao
2/Fio
2 less than or equal to 300 mm Hg under standard oxygen fulfilled the acute respiratory distress syndrome criteria under noninvasive ventilation within the first 24 hours. Their mortality rate was similar to that reported in the Berlin definition of acute respiratory distress syndrome. Therefore, spontaneous breathing patients with the acute respiratory distress syndrome criteria could be identified early without positive pressure ventilation.
Comparative Analysis of Ampicillin Plasma and Dried Blood Spot Pharmacokinetics in Neonates
Authors: Le Jennifer , Poindexter Brenda , Sullivan Janice E. , Laughon Matthew , Delmore Paula , Blackford Martha , Yogev Ram , James Laura P. , Melloni Chiara , Harper Barrie , Mitchell Jeff , Benjamin Daniel K. , Boakye-Agyeman Felix , Cohen-Wolkowiez Michael ,   On behalf of the Administrative Core Committee of the Best Pharmaceuticals for Children Act–Pediatric Trials Network
Published: December 2017

Background:
Dried blood spot (DBS) is a practical sampling strategy for pharmacokinetic studies in neonates. The utility of DBS to determine the population pharmacokinetics (pop-PK) of ampicillin, as well as accuracy versus plasma samples, was evaluated.

Methods:
An open-label, multicenter, opportunistic, prospective study was conducted in neonates. Ampicillin concentrations from plasma and DBS (CONCPlasma and CONCDBS) were measured by liquid chromatographic tandem mass spectrometry and analyzed using pop-PK and statistical (including transformation) approaches.

Results:
A total of 29 paired plasma and DBS samples from 18 neonates were analyzed. The median (range) gestational age and postnatal age were 37 (27–41) weeks and 8 (1–26) days, respectively. The geometric mean of CONCDBS to CONCPlasma ratio was 0.56. Correlation analysis demonstrated strong association between CONCPlasma and CONCDBS (r
2 = 0.902, analysis of variance P < 0.001). Using linear regression transformation, the estimated CONCPlasma (eCONCPlasma) was derived using (CONCDBS − 3.223)/0.51. The median bias and geometric mean ratio improved to −11% and 0.88 (Wilcoxon signed-rank test, P < 0.001), respectively, when comparing eCONCPlasma to CONCPlasma. Furthermore, using pop-PK modeling, the median bias (interquartile range) for clearance and individual predicted concentrations improved to 8% (−11 to 50) and −8% (−34 to 11), respectively, when eCONCPlasma was used.

Conclusions:
After transformation, DBS sampling accurately predicted ampicillin exposure in neonates.
Cohesin mutations in myeloid malignancies made simple
Authors: Viny Aaron D. , Levine Ross L. 
Published: December 2017

Purpose of review
Recurrent loss of function mutations within genes of the cohesin complex have been identified in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). STAG2 is the most commonly mutated cohesin member in AML as well as solid tumors. STAG2 is recurrently, mutated in Ewing's Sarcoma, bladder cancer, and glioblastoma, and is one of only ten genes known to be recurrently mutated in over four distinct tissue types of human cancer

Recent findings
The cohesin complex, a multiprotein ring, is canonically known to align and stabilize replicated chromosomes prior to cell division. Although initially thought to lead to unequal chromosomal separation in dividing cells, data in myeloid malignancies show this is not observed in cohesin mutant MDS/AML, either in large patient cohorts or mouse models. Mounting evidence supports a potential alternate mechanism whereby drivers of cell-type specific gene expression and hematopoietic development are impaired through alteration in three-dimensional nuclear organization and gene structure.

Summary
Understanding the functional consequences of cohesin mutations in regulating lineage-specific and signal-dependent defects and in myeloid transformation will identify novel pathophysiologic mechanisms of disease and inform the development of novel therapeutic targets.
The most novel of the novel agents for acute myeloid leukemia
Authors: Perl Alexander E. 
Published: December 2017

Purpose of review
Precious few drugs were successfully developed for acute myeloid leukemia (AML) over the past decades, despite a dramatic expansion of our understanding of its molecular underpinnings during this time. Then in 2017, a wave of new drugs suddenly became approved. This review serves to introduce the newly available drugs, discuss their impact upon therapy, and highlight additional novel agents that are waiting in the wings.

Recent findings
Newly approved agents in AML include a tyrosine kinase inhibitor for patients with FMS-like tyrosine kinase 3 (FLT3) mutations, an inhibitor of mutant isocitrate dehydrogenase (IDH2), and two novel agents using antibody-delivered or liposome-delivered cytotoxics. All of these new agents have demonstrable activity in AML and several have improved survival in randomized studies. In addition to these agents, promising data from other inhibitors of FLT3, IDH1, and B-cell lymphoma 2 (BCL2) will be discussed.

Summary
Response, survival, and symptom burden of AML therapy are all improving through novel agents. As many of the newly approved drugs benefit-specific genetic subsets, a new priority has emerged to increase the speed of diagnostic genomic studies as a means to guide frontline therapy. This will ensure patients are optimally categorized and treated with to the most rational agents.
The recurrent pleomorphic adenoma conundrum
Authors: Bradley Patrick J. 
Published: December 2017

Purpose of review
Recurrent pleomorphic adenoma (RPA) is uncommon. Treatment selection is based on the likely possibility of minimizing the risk of tumour recurrence, avoiding local functional and cosmetic sequelae, and eradicates the possibility of metastatic or malignant transformation. Much has changed since the topic was reviewed in 2001, and this manuscript comments on clinical progress and discusses patient treatment options.

Recent findings
Surgery is the preferred treatment for head and neck pleomorphic adenoma. Over the recent decade the surgical radicality is favoured for parotid and submandibular gland pleomorphic adenoma, from total gland and tumour removal to endoscopic or minimal open extracapsular tumour excision. Currently molecular pathology and biomarker research has not identified any evidence that separates pleomorphic adenoma from RPA, thus supporting that tumour recurrence is likely associated with surgery. Revision surgery has been reported to be frequently noncurative depending on the extent of the primary surgery, with the added risk of local cosmetic and functional sequelae. Radiotherapy as a nonsurgical modality has advanced and has been shown to be effective in controlling, if not curing, high-risk patients who have identifiable prognostic factors of developing a recurrence and patients with RPA.

Summary
Current surgical management of pleomorphic adenoma is associated with improved quality of life and minimal disturbance to cosmetic and functional. The reported incidence of RPA has been reduced by ‘expert surgeons’ but with limited short-term follow-up following more recent surgical modifications. Patients with RPA should be offered treatment that includes surgery and/or radiotherapy and should be encouraged to partake of this decision making process.
Oncologic and functional outcomes of patients treated with transoral CO2 laser microsurgery or radiotherapy for T2 glottic carcinoma: a systematic review of the literature
Authors: Hendriksma Martine , Heijnen Bas J. , Sjögren Elisabeth V. 
Published: December 2017

Purpose of review
To give an overview of the laryngeal preservation and functional outcomes of patients treated with transoral CO2 laser microsurgery (TLM) or radiotherapy for T2 glottic carcinoma. This information supports physicians and patients in treatment counselling and choices.

Recent findings
A recent systematic review showed that local control rates at 5-year did not differ between radiotherapy and TLM for T2 glottic tumours. However, there is a lack of comparative data on laryngeal preservation as well as functional outcomes in T2 glottic carcinoma.

Summary
Laryngeal preservation for T2 tumours in this review is higher for patients treated primarily with TLM (88.8 vs. 79.0%). It is important to differentiate between tumours with normal and impaired mobility (T2a and T2b) because the latter showed poorer prognosis for both TLM and radiotherapy. Involvement of the anterior commissure does not result in significantly lower oncological results, if adequately staged and treated. More studies are needed to support these data and to compare the functional outcomes between TLM and radiotherapy for T2 glottic carcinoma.
Reduction of Injection-Related Risk Behaviors After Emergency Implementation of a Syringe Services Program During an HIV Outbreak
Authors: Patel Monita R. , Foote Carrie , Duwve Joan , Chapman Erika , Combs Brittany , Fry Alexandra , Hall Patti , Roseberry Jeremy , Brooks John T. , Broz Dita 
Published: December 2017

Objective:
To describe injection-related HIV risk behaviors preimplementation and postimplementation of an emergency syringe services program (SSP) in Scott County, Indiana, after an HIV outbreak among persons who inject drugs (PWID).

Design:
Mixed methods retrospective pre–post intervention analysis.

Methods:
We analyzed routine SSP program data collected at first and most recent visit among clients with ≥2 visits, ≥7 days apart from April 4 to August 30, 2015, to quantify changes in injection-related risk behaviors. We also analyzed qualitative data collected from 56 PWID recruited in Scott County to understand factors contributing to these behaviors.

Results:
SSP clients included in our analysis (n = 148, 62% of all SSP clients) reported significant (P < 0.001) reductions over a median 10 weeks (range 1–23) in syringe sharing to inject (18%–2%) and divide drugs (19%–4%), sharing other injection equipment (eg, cookers) (24%–5%), and number of uses of the same syringe [2 (interquartile range: 1–4) to 1 (interquartile range: 1–1)]. Qualitative study participants described access to sterile syringes and safer injection education through the SSP, as explanatory factors for these reductions. Injection frequency findings were mixed, but overall suggested no change. The number of syringes returned by SSP clients increased from 0 at first visit to median 57. All qualitative study participants reported using sharps containers provided by the SSP.

Conclusions:
Analyses of an SSP program and in-depth qualitative interview data showed rapid reduction of injection-related HIV risk behaviors among PWID post-SSP implementation. Sterile syringe access as part of comprehensive HIV prevention is an important tool to control and prevent HIV outbreaks.
Treatment of severe skin and soft tissue infections: a review
Authors: Burnham Jason P. , Kollef Marin H. 
Published: December 2017

Purpose of review
To review the salient features of the management of severe skin and soft tissue infections (SSTIs), including toxic shock syndrome, myonecrosis/gas gangrene, and necrotizing fasciitis.

Recent findings
For severe SSTIs, intensive care, source control, and broad-spectrum antimicrobials are required for the initial phase of illness. There is an increasing focus on the utility of rapid diagnostic tests to help in selection and de-escalation of antimicrobials for SSTIs. In addition, clinical prediction scores have shown promise in helping predict patients who do not require antimicrobials directed against methicillin-resistant Staphylococcus aureus. Immune status has been shown to be important in clinical outcomes of some, but not all types of SSTIs. The debate for benefits of intravenous immunoglobulin continues to be waged in the recent literature.

Summary
Severe SSTIs are common and their management complex due to regional variation in predominant pathogens and antimicrobial resistance patterns, as well variations in host immune responses. Unique aspects of care for severe SSTIs are discussed including the role of surgical consultation and source control. The unique features of SSTIs in immunocompromised hosts are also described.
Discrepancies Between Alzheimer’s Disease Patients’ and Caregivers’ Ratings About Patients’ Quality of Life
Authors: Sousa Maria F.B. , Santos Raquel L. , Simões Pedro , Conde-Sala Josep L. , Dourado Marcia C.N. 
Published: December 2017

Objectives:
We investigated the factors associated with discrepancies between patients’ and caregivers’ ratings about patients’ general quality of life (QoL) and about the domains of Quality of Life in Alzheimer’s disease (QoL-AD) Scale at baseline and 12 months.

Methods:
This was a longitudinal study that comprised 114 outpatients with AD and their caregivers. Patients were assessed with the QoL-AD, Mini-mental State Examination, Assessment Scale of Psychosocial Impact of the Diagnosis of Dementia, Cornell Scale for Depression, Functional Activities Questionnaire, and Neuropsychiatric Inventory, and Clinical Dementia Rating Scale. Caregivers answered the QoL-AD, Zarit Burden Interview and Sociodemographic Questionnaire.

Results:
Linear regression analyses indicated that the factors associated with discrepancies of patients’ and caregivers’ ratings of patients’ QoL-AD were impaired awareness and caregiver burden at baseline and impaired awareness at 12 months. Moreover, the factor associated with discrepancies in the domain memory was impaired awareness and in the domain ability to do chores, impaired awareness and functional deficit.

Conclusions:
The discrepancies between patients and caregivers were related to awareness and caregiver burden at baseline and to awareness at 12 months. These results raise questions regarding the subjective nature of QoL and the validity of patients’ evaluation of their own QoL.
Trends, geographic variation, and factors associated with prescribing of gluten-free foods in English primary care: a cross sectional study
Authors: Walker Alex J , Curtis Helen J , Bacon Seb , Croker Richard , Goldacre Ben 
Published: December 2017

AbstractBackgroundThere is substantial disagreement about whether gluten-free foods should be prescribed on the NHS. We aim to describe time trends, variation and factors associated with prescribing gluten-free foods in England.MethodsWe described long-term national trends in gluten-free prescribing, and practice and Clinical Commissioning Group (CCG) level monthly variation in the rate of gluten-free prescribing (per 1000 patients) over time. We used a mixed effect poisson regression model to determine factors associated with gluten-free prescribing rate.ResultsThere were 1.3 million gluten-free prescriptions between July 2016 and June 2017, down from 1.8 million in 2012/13, with a corresponding cost reduction from £25.4m to £18.7m. There was substantial variation in prescribing rates among practices (range 0 to 148 prescriptions per 1000 patients, interquartile range 7.3 to 31.8), driven in part by substantial variation at the CCG level, likely due to differences in prescribing policy. Practices in the most deprived quintile of deprivation score had a lower prescribing rate than those in the highest quintile (incidence rate ratio 0.89, 95% confidence interval 0.87-0.91). This is potentially a reflection of the lower rate of diagnosed coeliac disease in more deprived populations.ConclusionGluten-free prescribing is in a state of flux, with substantial clinically unwarranted variation between practices and CCGs.Strengths and weaknesses of the studyWe were able to measure the prescribing of gluten-free foods across all prescribing in England, eliminating bias. We also removed seasonal variation by aggregating savings over 12 months.As well as gluten-free prescribing variation at practice and CCG level, we have described long-term prescribing trends at national level, back to 1998.Using the available data, we were unable to look at gluten-free prescribing at prescriber level, or investigate factors associated with prescribing to individual patients
Correct laminar positioning in the neocortex influences proper dendritic and synaptic development
Authors: Martineau Fanny Sandrine , Sahu Surajit , Plantier Vanessa , Buhler Emmanuelle , Schaller Fabienne , Fournier Lauriane , Chazal Geneviève , Kawasaki Hiroshi , Represa Alfonso , Watrin Françoise , Manent Jean-Bernard 
Published: December 2017

AbstractThe neocortex is a six-layered laminated structure with a precise anatomical and functional organization ensuring proper function. Laminar positioning of cortical neurons, as determined by termination of neuronal migration, is a key determinant of their ability to assemble into functional circuits. However, the exact contribution of laminar placement to dendrite morphogenesis and synapse formation remains unclear. Here we manipulated the laminar position of cortical neurons by knocking down Dcx, a crucial effector of migration, and show that misplaced neurons fail to properly form dendrites, spines and functional glutamatergic synapses. We further show that knocking down Dcx in properly positioned neurons induces similar but milder defects, suggesting that the laminar misplacement is the primary cause of altered neuronal development. Thus, the specific laminar environment of their fated layers is crucial for the maturation of cortical neurons, and influences their functional integration into developing cortical circuits.
PolNet Analysis: a software tool for the quantification of network-level endothelial cell polarity and blood flow during vascular remodelling
Authors: Bernabeu Miguel O. , Jones Martin L. , Nash Rupert W. , Pezzarossa Anna , Coveney Peter V. , Gerhardt Holger , Franco Claudio A. 
Published: December 2017

AbstractIn this paper, we present PolNet, an open source software tool for the study of blood flow and cell-level biological activity during vessel morphogenesis. We provide an image acquisition, segmentation, and analysis protocol to quantify endothelial cell polarity in entire in vivo vascular networks. In combination, we use computational fluid dynamics to characterise the haemodynamics of the vascular networks under study. The tool enables, for the first time, network-level analysis of polarity and flow for individual endothelial cells. To date, PolNet has proven invaluable for the study of endothelial cell polarisation and migration during vascular patterning, as demonstrated by our recent papers [1, 2]. Additionally, the tool can be easily extended to correlate blood flow with other experimental observations at the cellular/molecular level. We release the source code of our tool under the LGPL licence.