bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physiological properties of the lamina I spinoparabrachial neurons in the mouse
Authors: Allard Julien 
Published: February 2019

Key points
Spinal cord lamina I neurons receiving dense input from nociceptors and projecting to the parabrachial area at the ponto‐mesencephalic junction form the major ascending pain‐related pathway in rodents.
Lamina I spinoparabrachial (SPB) neurons have never been characterized in mice, despite the growing and extensive use of this species to understand the contribution of lamina I SPB neurons in chronic pain.
The electrophysiological properties of lamina I SPB neurons recorded here in anaesthetized mice are comparable to those of rat or cat, forming a nociceptive and thermoreceptive pathway. It was confirmed ‘on line’ that lamina I SPB neurons that normally encode noxious stimuli can receive input from low threshold mechanoreceptors in certain conditions. The present work indicates that the study of lamina I SPB neurons in vivo could take advantage of the use of genetically modified mice.
AbstractOngoing studies investigating the role of lamina I projection neurons in the generation of chronic pain are mainly based on the use of genetically modified mice. However, lamina I projection neurons have never been physiologically characterized in this species. The present work aimed to fill this gap, and to assess the effect of spinal ‘disinhibition’ that may occur in chronic pain states on the responses of these neurons to light touch. Seventy lamina I spinoparabrachial (SPB) neurons were characterized in anaesthetized mice. These neurons showed low central conduction velocities (<12.4 m s−1) and wide range of responses. Fifty‐six neurons responded equally to noxious mechanical and thermal (heat) stimuli (16% responded consistently to light touch). Modality‐specific neurons responded preferentially to thermal (cold) stimuli (n = 10) and pinch (n = 2), or specifically to heat (n = 2). Spinal bicuculline and strychnine application induced responses to brush in half of the neurons tested, confirming directly the potential connection between low threshold mechanoreceptors and nociceptive‐specific neurons, responsible for mechanical allodynia. Remarkably, the effect of the treatment was highly variable and apparently independent of the initial profile of the neurons. The present data confirm that mice lamina I SPB neurons have the expected characteristics to form a nociceptive and thermoreceptive pathway, but they constitute a highly heterogeneous group. The differential effect of spinal disinhibition observed here suggests that a subgroup of lamina I SPB neurons might be responsible for abnormal pain in pathological conditions, and emphasizes the importance of in vivo recording, a neglected approach.
Decisions and repercussions of second victim experiences for mothers in medicine (SAVE DR MoM)
Authors: Gupta Kiran , Lisker Sarah , Rivadeneira Natalie A , Mangurian Christina , Linos Eleni , Sarkar Urmimala 
Published: February 2019

BackgroundThe second victim effect is defined as emotional distress experienced by providers involved in mistakes. This study characterises events contributing to the second victim effect among a diverse sample of physician mothers, describes the impact on both provider and patient and seeks to determine the association between experiencing a mistake and burnout.MethodsIn this mixed-methods study, an anonymous, cross-sectional survey was posted to an online network of over 65 000 physician mothers on 17 June 2016. Self-reported involvement in a mistake provided opportunity to describe the error and impact on both provider and patient. Free-text responses were qualitatively coded to identify error types. Hypothesising that making a mistake contributes to burnout, self-reported burnout was examined using a single question. We used logistic regression to estimate the association between involvement in a mistake and burnout, adjusting for practice years, setting and specialty.Results5782 members completed the survey for an estimated response rate of 16.5% based on 34956 active users during the survey period. 2859 respondents reported involvement in a mistake (49%), which was associated with higher reported burnout (p<0.0001). 56% of those reporting a mistake provided descriptions. Qualitative analysis revealed that self-reported treatment errors were more common and diagnostic errors were most often reported to result in greater patient harm. Of those involved in a mistake, 82% reported feelings of guilt; 2.2% reported reducing clinical workload, taking leave or leaving the profession.ConclusionsPhysician mothers involved in errors experience negative outcomes and may be at increased risk for burnout. Additional research should focus on strategies to mitigate burnout associated with the second victim effect, particularly among women physicians and those with family responsibilities.
Physical activity and left ventricular trabeculation in the UK Biobank community-based cohort study
Authors: Woodbridge Simon P , Aung Nay , Paiva Jose M , Sanghvi Mihir M , Zemrak Filip , Fung Kenneth , Petersen Steffen E 
Published: February 2019

ObjectiveVigorous physical activity (PA) in highly trained athletes has been associated with heightened left ventricular (LV) trabeculation extent. It has therefore been hypothesised that LV trabeculation extent may participate in exercise-induced physiological cardiac remodelling. Our cross-sectional observational study aimed to ascertain whether there is a ‘dose–response’ relationship between PA and LV trabeculation extent and whether this could be identified at opposite PA extremes.MethodsIn a cohort of 1030 individuals from the community-based UK Biobank study (male/female ratio: 0.84, mean age: 61 years), PA was measured via total metabolic equivalent of task (MET) min/week and 7-day average acceleration, and trabeculation extent via maximal non-compaction/compaction ratio (NC/C) in long-axis images of cardiovascular magnetic resonance studies. The relationship between PA and NC/C was assessed by multivariate regression (adjusting for potential confounders) as well as between demographic, anthropometric and LV phenotypic parameters and NC/C.ResultsThere was no significant linear relationship between PA and NC/C (full adjustment, total MET-min/week: ß=−0.0008, 95% CI −0.039 to –0.037, p=0.97; 7-day average acceleration: ß=−0.047, 95% CI −0.110 to –0.115, p=0.13, per IQR increment in PA), or between extreme PA quintiles (full adjustment, total MET-min/week: ß=−0.026, 95% CI −0.146 to –0.094, p=0.67; 7-day average acceleration: ß=−0.129, 95% CI −0.299 to –0.040, p=0.49), across all adjustment levels. A negative relationship was identified between left ventricular ejection fraction and NC/C, significantly modified by PA (ß difference=−0.006, p=0.03).ConclusionsIn a community-based general population cohort, there was no relationship at, or between, extremes, between PA and NC/C, suggesting that at typical general population PA levels, trabeculation extent is not influenced by PA changes.
Predicting Survival in Patients Undergoing Resection for Locally Recurrent Retroperitoneal Sarcoma: A Study and Novel Nomogram from TARPSWG
Authors: Raut Chandrajit P. , Callegaro Dario , Miceli Rosalba , Barretta Francesco , Rutkowski Piotr , Blay Jean-Yves , Lahat Guy , Strauss Dirk C. , Gonzalez Ricardo , Ahuja Nita , Grignani Giovanni , Quagliuolo Vittorio , Stoeckle Eberhard , De Paoli Antonino , Pillarisetty Venu G. , Nessim Carolyn , Swallow Carol J. , Bagaria Sanjay , Canter Robert , Mullen John , Gelderblom Hans J. , Pennacchioli Elisabetta , van Coevorden Frits , Cardona Kenneth , Fiore Marco , Fairweather Mark , Gronchi Alessandro 
Published: February 2019

AbstractPurpose:The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram.Experimental Design:Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002–2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index).Results:Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80–169] from initial surgery and 75 months (IQR 50–105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0–23.0%] and 54.1% (95% CI, 49.8–58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%–70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively).Conclusions:We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.
A Phase II Randomized Study of Neoadjuvant Letrozole Plus Alpelisib for Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer (NEO-ORB)
Authors: Mayer Ingrid A. , Prat Aleix , Egle Daniel , Blau Sibel , Fidalgo J. Alejandro Pérez , Gnant Michael , Fasching Peter A. , Colleoni Marco , Wolff Antonio C. , Winer Eric P. , Singer Christian F. , Hurvitz Sara , Estévez Laura García , van Dam Peter A. , Kümmel Sherko , Mundhenke Christoph , Holmes Frankie , Babbar Naveen , Charbonnier Laure , Diaz-Padilla Ivan , Vogl Florian D. , Sellami Dalila , Arteaga Carlos L. 
Published: February 2019

Abstract

Purpose:
Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA-mutant, hormone receptor–positive (HR+) advanced/metastatic breast cancer in the phase III SOLAR-1 study. The combination of alpelisib and letrozole also had promising activity in phase I studies of HR+ advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting.
Patients and Methods: Postmenopausal women with HR+, human epidermal growth factor receptor 2-negative, T1c-T3 breast cancer were assigned to the PIK3CA-wild-type or PIK3CA-mutant cohort according to their tumor PIK3CA status, and randomized (1:1) to 2.5 mg/day letrozole with 300 mg/day alpelisib or placebo for 24 weeks. Primary endpoints were objective response rate (ORR) and pathologic complete response (pCR) rate for both PIK3CA cohorts.

Results:
In total, 257 patients were assigned to letrozole plus alpelisib (131 patients) or placebo (126 patients). Grade ≥3 adverse events (≥5% of patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculo-papular rash (8%). The primary objective was not met; ORR in the alpelisib versus placebo arm was 43% versus 45% and 63% versus 61% in the PIK3CA-mutant and wild-type cohorts, respectively. pCR rates were low in all groups. Decreases in Ki-67 were similar across treatment arms and cohorts. In PIK3CA-mutant tumors, alpelisib plus letrozole treatment induced a greater decrease in phosphorylated AKT versus placebo plus letrozole.

Conclusions:
In contrast to initial results in advanced/metastatic disease, addition of alpelisib to 24-week neoadjuvant letrozole treatment did not improve response in patients with HR+ early breast cancer.
A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women
Authors: Jiao Li , Maity Suman , Coarfa Cristian , Rajapakshe Kimal , Chen Liang , Jin Feng , Putluri Vasanta , Tinker Lesley F. , Mo Qianxing , Chen Fengju , Sen Subrata , Sangi-Hyghpeykar Haleh , El-Serag Hashem B. , Putluri Nagireddy 
Published: February 2019

Abstract
To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case–control targeted metabolomics study using prediagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the LC/MS to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired t test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference. FDR adjusted q-value &lt; 0.25 was indicated statistically significant. Logistic regression model and ROC curve analysis were used to evaluate the clinical utility of the metabolites. Among 30 case/control pairs, 1-methyl-l-tryptophan (L-1MT) was significantly lower in the cases than in the controls (log2 FC = −0.35; q-value = 0.03). The area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer.
Multiple Approaches to Diffusion Magnetic Resonance Imaging in Hereditary Cerebral Amyloid Angiopathy Mutation Carriers
Authors: Schouten Tijn M. , de Vos Frank , van Rooden Sanneke , Bouts Mark J. R. J. , van Opstal Anna M. , Feis Rogier A. , Terwindt Gisela M. , Wermer Marieke J. H. , van Buchem Mark A. , Greenberg Steven M. , de Rooij Mark , Rombouts Serge A. R. B. , van der Grond Jeroen 
Published: February 2019

Background

Cerebral amyloid angiopathy (
CAA
) is a major cause of lobar intracerebral hemorrhage in elderly adults; however, presymptomatic diagnosis of
CAA
is difficult. Hereditary cerebral hemorrhage with amyloidosis–Dutch type (
HCHWA
‐D) is a rare autosomal‐dominant disease that leads to pathology similar to sporadic
CAA
. Presymptomatic
HCHWA
‐D mutation carriers provide a unique opportunity to study
CAA
‐related changes before any symptoms have occurred. In this study we investigated early
CAA
‐related alterations in the white matter.

Methods and Results

We investigated diffusion magnetic resonance imaging (
dMRI
) data for 15 symptomatic and 11 presymptomatic
HCHWA
‐D mutation carriers and 30 noncarrier control participants using 4 different approaches. We looked at (1) the relation between age and global
dMRI
measures for mutation carriers versus controls, (2) voxel‐wise d
MRI
, (3) independent component‐clustered
dMRI
measures, and (4) structural connectomics between presymptomatic or symptomatic carriers and controls. Fractional anisotropy decreased, and mean diffusivity and peak width of the skeletonized mean diffusivity increased significantly over age for mutation carriers compared with controls. In addition, voxel‐wise and independent component‐wise fractional anisotropy, and mean diffusivity, and structural connectomics were significantly different between
HCHWA
‐D patients and control participants, mainly in the periventricular frontal and occipital regions and in the occipital lobe. We found no significant differences between presymptomatic carriers and control participants.

Conclusions

The d
MRI
technique is sensitive in detecting alterations in symptomatic
HCHWA
‐d carriers but did not show alterations in presymptomatic carriers. This result indicates that d
MRI
may be less suitable for identifying early white matter changes in
CAA
.
A Revisit of Infinite Population Models for Evolutionary Algorithms on Continuous Optimization Problems
Authors: Song Bo , Li Victor O.K. 
Published: February 2019

AbstractInfinite population models are important tools for studying population dynamics of evolutionary algorithms. They describe how the distributions of populations change between consecutive generations. In general, infinite population models are derived from Markov chains by exploiting symmetries between individuals in the population and analyzing the limit as the population size goes to infinity. In this article, we study the theoretical foundations of infinite population models of evolutionary algorithms on continuous optimization problems. First, we show that the convergence proofs in a widely cited study were in fact problematic and incomplete. We further show that the modeling assumption of exchangeability of individuals cannot yield the transition equation. Then, in order to analyze infinite population models, we build an analytical framework based on convergence in distribution of random elements which take values in the metric space of infinite sequences. The framework is concise and mathematically rigorous. It also provides an infrastructure for studying the convergence of the stacking of operators and of iterating the algorithm which previous studies failed to address. Finally, we use the framework to prove the convergence of infinite population models for the mutation operator and the k-ary recombination operator. We show that these operators can provide accurate predictions for real population dynamics as the population size goes to infinity, provided that the initial population is identically and independently distributed.
Implications of Improved Representation of Convection for the East Africa Water Budget Using a Convection-Permitting Model
Authors: Finney Declan L. , Marsham John H. , Jackson Lawrence S. , Kendon Elizabeth J. , Rowell David P. , Boorman Penelope M. , Keane Richard J. , Stratton Rachel A. , Senior Catherine A. 
Published: February 2019

Abstract
The precipitation and diabatic heating resulting from moist convection make it a key component of the atmospheric water budget in the tropics. With convective parameterization being a known source of uncertainty in global models, convection-permitting (CP) models are increasingly being used to improve understanding of regional climate. Here, a new 10-yr CP simulation is used to study the characteristics of rainfall and atmospheric water budget for East Africa and the Lake Victoria basin. The explicit representation of convection leads to a widespread improvement in the intensities and diurnal cycle of rainfall when compared with a parameterized simulation. Differences in large-scale moisture fluxes lead to a shift in the mean rainfall pattern from the Congo to Lake Victoria basin in the CP simulation—highlighting the important connection between local changes in the representation of convection and larger-scale dynamics and rainfall. Stronger lake–land contrasts in buoyancy in the CP model lead to a stronger nocturnal land breeze over Lake Victoria, increasing evaporation and moisture flux convergence (MFC), and likely unrealistically high rainfall. However, for the mountains east of the lake, the CP model produces a diurnal rainfall cycle much more similar to satellite estimates, which is related to differences in the timing of MFC. Results here demonstrate that, while care is needed regarding lake forcings, a CP approach offers a more realistic representation of several rainfall characteristics through a more physically based realization of the atmospheric dynamics around the complex topography of East Africa.
Receiving Social Support after Short-term Confinement: How Support Pre- and During-confinement Contribute
Authors: Hickert Audrey , Palmen Hanneke , Dirkzwager Anja , Nieuwbeerta Paul 
Published: February 2019

Objectives: To test the independent links between social support that exists prior to and during confinement with support after release for adult males incarcerated for an average of 11 months in the Netherlands. Methods: Longitudinal data from a large study on consequences of confinement, the Prison Project, are used to describe instrumental (live with) and expressive (core network) support before and after confinement from four sources (parent, partner, other family, friend) and during-confinement visits by the same groups. Multiequation models examine the contribution of preconfinement support and visits to postconfinement support, while also describing the interrelationship of support sources. Results: Preconfinement support is consistently related to receiving the same type after release. Receiving visits during confinement has a unique relationship with receiving postconfinement expressive support across all relational groups. Only visits from partners has an additional influence on instrumental support after release. Postconfinement support across provider groups is interrelated, with a positive correlation across providers for expressive support and a substitution effect for instrumental support between parents and partners. Conclusions: After controlling for important preconfinement differences in support, visits remain significantly related to postconfinement expressive support, suggesting a possible mechanism by which visits help improve reentry outcomes.
Singulars, Plurals, and Section 57 of the Constitution
Authors: Sawer Geoffrey 
Published: February 2019

Whether words in the singular include the plural or whether words in the plural include the singular is a common problem of statutory interpretation. Acts interpretation legislation of the States and the Commonwealth offer slightly varying presumptions for dealing with the problem. Professor Sawer analyses these presumptions and their application in numerous cases. As well, reforms that would lead to greater clarity and uniformity of such legislation are suggested.The second part of the article explores the special problems regarding singulars and plurals in the context of the Constitution and, in particular, section 57 which provides for the resolution of deadlocks between the Senate and the House of Representatives with regard to “any proposed law”. The High Court's resolution of some of the problems raised when more than one proposed law is the subject of disagreement between the Houses of Parliament is exhaustively analysed. In addition, solutions are offered to a number of judicially unanswered questions relating to section 57 of the Constitution.
Basaloid Squamous Cell Carcinoma of the Larynx: A National Cancer Database Analysis
Authors: Jumaily Mejd , Faraji Farhoud , Zhang Donald , Walker Ronald J. , Ward Gregory M. 
Published: February 2019

ObjectiveBasaloid squamous cell histology is a rare variant that accounts for about 2% of all head and neck squamous cell laryngeal carcinomas. The purpose of this study was to examine overall survival rates of patients according to treatment, stage, and laryngeal subsite.Study DesignRetrospective analysis.SettingNational Cancer Database (NCDB).Subjects and MethodsThe NCDB was queried for patients with basaloid squamous cell carcinoma (BSCC) who were treated from 2004 to 2014. Five‐year overall survival rates were determined by the Kaplan‐Meier method. Univariate and multivariate analysis was used to identify factors correlated with 5‐year overall survival.ResultsThe NCDB identified 440 patients meeting inclusion criteria. Median follow‐up time was 31.2 months. On univariate analysis, the treatment modalities assessed (surgery alone, surgery with radiotherapy, surgery with chemoradiotherapy, radiotherapy, chemoradiotherapy) did not differ in their survival benefit. On multivariate analysis, only chemoradiotherapy (hazard ratio, 0.587; 95% CI, 0.37‐0.93; P =. 022) was associated with improved survival. All treatment modalities performed similarly between stage I and II tumors (P =. 340) and stage III and IV tumors (P =. 154).ConclusionThis study represents the largest laryngeal BSCC series to date. We found that chemoradiotherapy was associated with improved 5‐year overall survival of laryngeal BSCC on multivariate analysis.