bluuebunny/crossref_metadata_2025_split huggingface dataset:
Training Methods for Delivering Difficult News in Genetic Counseling and Genetics Residency Training Programs
Authors: Andoni Laila , Hobson Wendy L. , Carey John C. , Dent Karin M. 
Published: June 2018

AbstractGenetic counselors and clinical geneticists are often in the position of delivering difficult news (DDN) to patients and families. Many studies show that healthcare providers require major improvement in the skills needed in DDN in a manner that is satisfactory to their patients. The purpose of this study was to assess the amount and methodology of DDN training received by genetic counselors and medical genetics residents in their training programs, such as observations of DDN or attending didactic lectures. To our knowledge, there is no previous assessment or study of DDN training in genetic counselor and medical genetics residency programs; therefore, we aim to both assess and compare the training in DDN received by genetic counselors and by genetics residents and determine whether there is a desire for recommendations on DDN training. We invited genetic counseling (GC) and genetics residency program directors to participate in an online survey designed to assess coursework, clinical experiences, and directors’ attitudes toward teaching DDN. Response rate was 85% (28/33) for GC program directors and 26% (14/53) for genetics residency program directors. One hundred percent of GC and genetics residency directors who responded to the survey agreed that it is important for genetic counselors and medical geneticists to be able to deliver difficult news effectively and that training programs should formally teach students how to deliver difficult news. Six of the eight common teaching methods are used by at least 75% of GC programs while two of eight are used by at least 75% of genetics residency programs. Seventy‐nine percent of GC and 93% of genetics residency program directors agree that there should be recommendations on how to teach students to deliver this news. Our results show that techniques for DDN are integrated more fully into GC program curricula than genetics residency curricula. Directors of both types of programs desire recommendations and more standardized education for training students to deliver difficult news.
Is Total Femur Replacement a Reliable Treatment Option for Patients With Metastatic Carcinoma of the Femur?
Authors: Sevelda Florian , Waldstein Wenzel , Panotopoulos Joannis , Kaider Alexandra , Funovics Philipp Theodor , Windhager Reinhard 
Published: June 2018

Abstract

Background
The majority of metastatic bone lesions to the femoral bone can be treated without surgery or with minimally invasive intramedullary nailing. In rare patients with extensive metastatic disease to the femur, total femur replacement may be the only surgical alternative to amputation; however, little is known about this approach.

Questions/purposes
In a highly selected small group of patients with metastatic carcinoma of the femur, we asked: (1) What was the patient survivorship after this treatment? (2) What was the implant survivorship free from all-cause revision and amputation, and what complications were associated with this treatment? (3) What functional outcomes were achieved by patients after total femur replacement for this indication?

Methods
Eleven patients (three men, eight women) with a mean age of 64 years (range, 41-78 years) received total femur replacements between 1986 and 2016; none were lost to followup. The most common primary disease was breast cancer. In general, during this period, our indications for this procedure were extensive metastatic disease precluding internal fixation or isolated proximal or distal femur replacement, and an anticipated lifespan exceeding 6 months. Our contraindication for this procedure during this time was expected lifespan less than 6 months. Patient survival was assessed by Kaplan-Meier analysis; implant survival free from revision surgery and amputation were assessed by competing risk analysis. Function was determined preoperatively and 6 to 12 weeks postoperatively with the Musculoskeletal Tumor Society (MSTS) score normalized to a 100-point scale, with higher scores representing better function from a longitudinally maintained institutional database.

Results
Eleven patients died at a median of 5 months (range, 1-31 months) after surgery. One-year revision-free and limb survival were 82% (95% CI, 51%-98%) and 91% (95% CI, 61%-99%), respectively. Reasons for reoperation were hip dislocation, infection and local recurrence in one patient each. The latter two complications resulted in amputation in two patients. The median MSTS score was 32 (range, 13-57).

Conclusions
Despite attempts to select patients who might have anticipated greater life expectancy, eight of 11 patients died by 6 months after surgery, and an additional two patients had undergone an amputation at 8 and at 17 months postoperatively. Most patients undergoing total femur replacement in this series did not recover from the procedure by the time they died, despite our best attempts to perform the procedure in patients whom we thought would live at least 6 months. Based on this, we believe that most patients with extensive metastatic disease to the femur should be offered palliative care, rather than major reconstruction.

Level of Evidence
Level IV, therapeutic study
Reduced-Order Microstructure-Sensitive Models for Damage Initiation in Two-Phase Composites
Authors: Montes de Oca Zapiain David , Popova Evdokia , Abdeljawad Fadi , Foulk James W. , Kalidindi Surya R. , Lim Hojun 
Published: June 2018

AbstractLocal features of the internal structure or the microstructure dominate the overall performance of materials. An open problem in materials design with enhanced properties is to accurately identify and quantify salient features of the microstructure and understand its correlation with the material’s performance. This task is exacerbated when dealing with failure related properties that show strong correlations to higher-order details of the material microstructure. This paper presents a novel data-driven framework for quantitatively determining the highly complex correlations that exist between the higher-order details of the material microstructure and its failure-related properties, specifically its damage initiation properties. The enclosed work will address this challenge by significantly extending the Materials Knowledge Systems (MKS) framework and by leveraging concepts in extreme value distributions and machine learning. The developed framework was capable of successfully sorting nine different classes of synthetically generated two-phase microstructures for their sensitivity to damage initiation. The framework and approaches presented here open new research avenues for studying the microstructure-sensitive damage initiation properties associated with heterogeneous materials, and pave the way forward for practical multiscale materials design.
Investigations of synthetic jet control effects on helicopter rotor in forward flight based on the CFD method
Authors: Zhao Q.-J. , Chen X. , Ma Y.-Yang , Zhao G.-Q. 
Published: June 2018

ABSTRACTTo investigate the control effect of the synthetic jet on the aerodynamic characteristic of rotors, a numerical simulation procedure for the rotor flowfield is established. First, a moving-embedded grid method and an unsteady Reynolds Averaged Navier–Stokes (URANS) solver are established for predicting the complex flowfield of rotors. A velocity jet boundary condition over the jet actuator orifice is constructed, and a numerical method for simulating the active flow control on rotors is developed. Then, the effectiveness of the simulation method is validated by comparing the numerical results of jet control on NACA 0015 aerofoil with the experimental data. At last, the aerodynamic characteristic of rotors with synthetic jet actuators located on the suction surface of the blade in forward flight is calculated. The results indicate that the synthetic jet has the capability of improving the aerodynamic characteristic of rotors, especially in inhibiting the flow separation over the surface. In addition, the increase of the jet momentum coefficient and the jet angle can both enhance the lift coefficient in the retreating side. Compared with a single jet, jet arrays have better control effects on improving the aerodynamic characteristic of rotors in forward flight.
P.048 Correlation of preoperative serum lactate, MR spectroscopy and frozen tissue lactate levels as a biomarker for giomas – a prospective clinical study
Authors: Khan OH , Nolt JK , Cousins JP , Agnihotri S , Vachhrajani S , Venkatraghavan L , Zadeh G 
Published: June 2018

Background: Lactate, a by-product of glycolysis, has been well established as a marker of poor tissue perfusion. Elevated lactate production is observed in tumor glycolysis known as the Warburg effect. We have previously shown that serum lactate correlated with brain tumor grade. In this prospective study we aimed to determine if the preoperative serum lactate correlated with preoperative MR spectroscopy and in lactate levels in the fresh frozen tissue samples. Methods: Twenty-one glioma patients (13 male, 8 female) ages 34 – 86 underwent craniotomy at a single institution by lead author. Tumor pathology revealed a Glioblastoma (n=16), grade II (oligodendroglioma n=1) and Grade III Glioma (anaplastic astrocytoma n=4). Preoperative spectroscopy was performed on 18 patients. A fellowship trained neuro-radiologist (JPC) was blinded to the serum and tissue lactate levels and graded the spectroscopy lactate levels as low or elevated. Results: There was direct correlation of spectroscopy tissue lactate levels with serum lactate levels. Pre-operative serum lactate (range 6.6- 29.9 mg/dl) was directly correlated with the fresh frozen tissue lactate levels (range 0.1 – 0.39 ug/mg; Pearson r=0.6 p = 0.0021). Conclusions: This study supports that serum lactate correlates with spectroscopy and tissue lactate levels.
P.070 Autosomal dominant MARS mutation linked to severe early onset CMT2U
Authors: McMillan HJ , Gillespie MK , Kernohan KD , Myer-Schuman R , Antonellis A , Boycott KM 
Published: June 2018

Background: Methionyl-tRNA synthetase (MARS) links methionine to its cognate tRNA required for translation. MARS mutations have been linked to adult-onset CMT2U. Methods: The proband had weakness in her first year of life, sitting at 11 months and walking at 20 months old. At 4 years old she was areflexic with distal > proximal weakness. Nerve conduction studies showed normal median and sural sensory responses with absent common peroneal, low median and tibial motor amplitudes. EMG noted denervation and quadriceps biopsy revealed neurogenic atrophy. Genetic testing for spinal muscular atrophy and sequencing of MNF2, RAB7A, LMNA, MPZ, HSPB1, NEFL, GADP1, TRPV4, HSPB8, GJB1 and PLEK8G5 were negative. She stopped walking at 9 years old and could not raise her arms above her head at 11 years old. Results: Exome sequencing identified MARS: c.1189G>A; p.Ala397Thr. To determine the functional consequences of p.A397T-MARS, yeast complementation assays were performed. Wild type or mutant MARS were cloned into yeast lacking the endogenous MARS ortholog. Wild-type MARS supported robust cellular growth, while the p.A397T-MARS insert did not support cellular growth confirming deleterious effect of this variant. Conclusions: Our patient’s phenotype was similar to children with motor-predominant GARS mutations. Functional data notes this MARS variant to be damaging and predictive of a severe, early-onset phenotype.
B.05 Nusinersen in infants who initiate treatment in a presymptomatic stage of spinal muscular atrophy (SMA): interim results from the Phase 2 NURTURE study
Authors: De Vivo DC , Bertini E , Hwu W , Foster R , Bhan I , Gheuens S , Farwell W , Reyna SP , Vajsar J 
Published: June 2018

Background: NURTURE (NCT02386553) is an ongoing open-label single-arm efficacy/safety study of intrathecal nusinersen in infants who initiate treatment in a presymptomatic stage of spinal muscular atrophy (SMA). Methods: Enrolled infants were age ≤6 weeks at first dose, clinically presymptomatic, had genetically diagnosed SMA, and 2 or 3 copies of SMN2. Primary endpoint is time to death or respiratory intervention (≥6 hours/day continuously for ≥7 days or tracheostomy). Results: As of July 5, 2017, 25 infants (2 copies SMN2, n=15;3 copies, n=10) were enrolled. All infants were alive. Two infants (both with 2 copies SMN2) required respiratory intervention (but not tracheostomy or permanent ventilation) during an acute, reversible viral infection and thus met the primary -endpoint. At last visit, 22/24 (92%) infants had achieved WHO motor milestones sitting without support and 8/16 (50%;2 SMN2, n=3/11;3 SMN2, n=5/5) on study >13 months achieved walking alone. AEs were reported in 24/25 (96%) infants; most 20/25 (80%) had AEs that were mild/moderate in severity; 9 had serious AEs. Four infants had an AE possibly related to study drug, which resolved despite continued treatment. No new safety concerns were identified. Conclusions: Nusinersen continued to benefit infants who initiated treatment in a presymptomatic stage of SMA.Study Support: Biogen
B.06 Safety and efficacy of nusinersen in infants/children with spinal muscular atrophy (SMA): part 1 of the phase 2 EMBRACE study
Authors: Shieh PB , Acsadi G , Mueller-Felber W , Crawford TO , Richardson R , Natarajan N , Castro D , Gheuens S , Bhan I , Gambino G , Sun P , Farwell W , Reyna SP , Vajsar J 
Published: June 2018

Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.Study Supported by: Ionis and Biogen
Area change of glaciers across Northern Ellesmere Island, Nunavut, between ~1999 and ~2015
Authors: WHITE ADRIENNE , COPLAND LUKE 
Published: June 2018

ABSTRACTUsing a variety of optical satellite scenes, this study quantifies the change in the areal extent of 1773 glaciers across Northern Ellesmere Island between ~1999 and ~2015. Our results show that the regional ice coverage decreased by 1705.3 km2over the ~16-year period, a loss of ~5.9%. Ice shelves had the greatest losses relative to their size, of ~42.4%. Glaciers feeding into ice shelves reduced in area by 4.7%, while tidewater glaciers reduced in area by 3.3%. Marine-terminating glaciers with floating ice tongues reduced in area by 4.9%, and 19 of these 27 ice tongues disintegrated, causing these glaciers to retreat to their grounding lines. Land-terminating glaciers lost 4.9% of their 1999 area, including the complete loss of three small ice caps (<1.5 km2). Our study highlights the high sensitivity of the ice cover of Northern Ellesmere Island to recent climate warming and the continued losses that are likely to occur in the future. In particular, the ice masses most susceptible to further losses are marine-terminating glaciers with floating termini and small land-terminating ice caps at low elevations.
Nutritional status and human milk intake of exclusively breast-fed infants at high altitude in La Paz, Bolivia
Authors: Urteaga Noelia , San Miguel José Luis , Aguilar Ana María , Muñoz Maruska , Slater Christine 
Published: June 2018

AbstractBreast-feeding habits are related to the nutritional status and the risk of illness and death in children under 2 years of age. For the first 6 months, infants should be exclusively breast-fed. This study aimed to evaluate the relationship between the infant’s nutritional status and human milk intake by breast-fed infants at high altitude. A quantitative, descriptive, correlational study was conducted including mother/baby pairs of infants aged 2–6 months. The amount of human milk consumed by the infants was assessed by the deuterium oxide dose-to-mother technique. The lipid content of human milk was measured by creamatocrit, and anthropometric measurements were performed. A total of eighteen mother/baby pairs were assessed. The mean human milk intake was 888 (sd 149) g/d, and the intake of water from other sources was 24·3 (sd 29·8) g/d. The lipid content in human milk was 41 (sd 12) g/l. The infant’s nutritional indicators were normal in all cases. A moderate positive correlation was found between milk volume and z scores weight-for-length r 0·58 (P=0·01), BMI-for-age r 0·56 (P=0·01) and weight-for-age r 0·45 (P=0·05). There was no correlation with length-for-age z score. The mean of breast milk intake in this study was similar to that found in other studies in the world. The lipid content is comparable to similar studies and was within the normal range. Children older than 3 months showed signs of stunting despite adequate volume and lipid content of breast milk.
Phytic acid improves intestinal mucosal barrier damage and reduces serum levels of proinflammatory cytokines in a 1,2-dimethylhydrazine-induced rat colorectal cancer model
Authors: Liu Cuiping , Chen Chen , Yang Fuguo , Li Xin , Cheng Lixue , Song Yang 
Published: June 2018

AbstractPhytic acid (PA) has been demonstrated to have a potent anticarcinogenic activity against colorectal cancer (CRC). Defects of the intestinal mucosal barrier and inflammation processes are involved in the development and progression of CRC. In the present study, we evaluated the effect of PA on the intestinal mucosal barrier and proinflammatory cytokines. After a 1-week acclimatisation period, sixty Wistar male rats were divided into the following five groups, with twelve rats per group: the control group (CG), model group (MG), low-PA-dose group (0·25 g/kg per d), middle-PA-dose group (0·5 g/kg per d), and high-PA-dose group (1 g/kg per d). 1,2-Dimethylhydrazine (DMH) at a dosage of 30 mg/kg of body weight was injected weekly to induce CRC for 18 weeks. We examined the expression of genes related to the intestinal mucosal barrier in the model. The results demonstrated that tumour incidence was decreased following PA treatment. The mRNA and protein expression of mucin 2 (MUC2), trefoil factor 3 (TFF3) and E-cadherin in the MG were significantly lower than those in the CG (P<0·05). The mRNA and protein expression of claudin-1 in the MG were significantly higher than those in the CG (P<0·05). PA elevated the mRNA and protein expression of MUC2, TFF3 and E-cadherin, and diminished the mRNA and protein expression of claudin-1. Furthermore, PA decreased serum levels of proinflammatory cytokines, which included TNF-α, IL-1βand IL-6. In conclusion, this study suggests that PA has favourable effects on the intestinal mucosal barrier and may reduce serum proinflammatory cytokine levels.
Reforming Everywhere and All at Once: Transitioning to Free Labor across the British Empire, 1837–1838
Authors: Boehme Kate , Mitchell Peter , Lester Alan 
Published: June 2018

AbstractIn late 1837 and early 1838 the British imperial government was preparing for an empire-wide transition from bonded to nominally free labor. This article builds upon recent scholarship that promotes a holistic, global approach to this transition, by narrowing the temporal frame and expanding the spatial. We emphasize interconnectivity and simultaneity rather than chronological succession, and we analyze the governance, rather than the experience, of this transition. Our approach is founded upon analysis of correspondence passing from every British colonial site through the Colonial Office in 1837–1838. We suggest that this hub of imperial government sought to reconcile the persistence of different conditions in each colony with the pursuit of three overarching policy objectives: redistributing labor globally; distinguishing between the moral debts owed to different kinds of bonded labor, and managing tradeoffs between security, economy, and morality. We conclude that the governance of the transition to free labor is best conceived as an assemblage of material and expressive elements of different spatial scales, whose interactions were complex and indeterminate. Through these specific governmental priorities and a particular communications infrastructure, these elements were brought into critical alignment at this moment to shape a significant transition in relations between people across the world.
Access to awareness of direct gaze is related to autistic traits
Authors: Madipakkam Apoorva Rajiv , Rothkirch Marcus , Dziobek Isabel , Sterzer Philipp 
Published: June 2018

AbstractBackgroundThe atypical processing of eye contact is a characteristic hallmark of autism spectrum disorder (ASD). The severity of these symptoms, however, is thought to lie on a continuum that extends into the typical population. While behavioural evidence shows that differences in social cognitive tasks in typically developed (TD) adults are related to the levels of autistic-like traits, it remains unknown whether such a relation exists for the sensitivity to direct gaze.MethodsIn two experiments, we measured reaction times to detect the faces with direct and averted gaze, suppressed from awareness, i.e. the access to awareness. In experiment 1, we tested N = 19 clinically diagnosed adults with ASD and N = 22 TD matched controls, while in experiment 2, we tested an independent sample of N = 20 TD adults.ResultsIn line with the literature, experiment 1 showed preferential processing of direct gaze in the TD group but not in the ASD group. Importantly, we found a linear relationship in both experiments between the levels of autistic traits within the groups of TD participants and their sensitivity to direct gaze: with increasing autistic characteristics, there was a decrease in sensitivity to direct gaze.ConclusionThese results provide the first evidence that differences in gaze processing and the sensitivity to direct gaze are already present in individuals with subclinical levels of autistic traits. Furthermore, they lend support to the continuum view of the disorder and could potentially help in an earlier diagnosis of individuals at high risk for autism.