bluuebunny/crossref_metadata_2025 huggingface dataset:
How does preclinical laboratory training impact physical examination skills during the first clinical year? A retrospective analysis of routinely collected objective structured clinical examination scores among the first two matriculating classes of a reformed curriculum in one Polish medical school
Authors: Świerszcz Jolanta , Stalmach-Przygoda Agata , Kuźma Marcin , Jabłoński Konrad , Cegielny Tomasz , Skrzypek Agnieszka , Wieczorek-Surdacka Ewa , Kruszelnicka Olga , Chmura Kaja , Chyrchel Bernadeta , Surdacki Andrzej , Nowakowski Michał
Published: September 2017

Objective

As a result of a curriculum reform launched in 2012 at our institution, preclinical training was shortened to 2 years instead of the traditional 3 years, creating additional incentives to optimise teaching methods. In accordance with the new curriculum, a semester-long preclinical module of clinical skills (CS) laboratory training takes place in the second year of study, while an introductory clinical course (ie, brief introductory clerkships) is scheduled for the Fall semester of the third year. Objective structured clinical examinations (OSCEs) are carried out at the conclusion of both the preclinical module and the introductory clinical course. Our aim was to compare the scores at physical examination stations between the first and second matriculating classes of a newly reformed curriculum on preclinical second-year OSCEs and early clinical third-year OSCEs.

Design

Analysis of routinely collected data.

Setting

One Polish medical school.

Participants

Complete OSCE records for 462 second-year students and 445 third-year students.

Outcome measures

OSCE scores by matriculation year.

Results

In comparison to the first class of the newly reformed curriculum, significantly higher (ie, better) OSCE scores were observed for those students who matriculated in 2013, a year after implementing the reformed curriculum. This finding was consistent for both second-year and third-year cohorts. Additionally, the magnitude of the improvement in median third-year OSCE scores was proportional to the corresponding advancement in preceding second-year preclinical OSCE scores for each of two different sets of physical examination tasks. In contrast, no significant difference was noted between the academic years in the ability to interpret laboratory data or ECG — tasks which had not been included in the second-year preclinical training.

Conclusion

Our results suggest the importance of preclinical training in a CS laboratory to improve students’ competence in physical examination at the completion of introductory clinical clerkships during the first clinical year.
Early interventions for the prevention of post-traumatic stress symptoms in survivors of critical illness: protocol for a systematic review
Authors: Glaspey Lindsey J , Roberts Michael B , Mazzarelli Anthony , Trzeciak Stephen , Roberts Brian W
Published: September 2017

Introduction

Post-traumatic stress disorder (PTSD) is being increasingly reported among survivors of critical illness and injury. Previous work has demonstrated that PTSD reduces patient quality of life and ability to return to work, as well as increases healthcare costs. As such, identifying interventions aimed at preventing the development of critical illness-related PTSD could have an important public health impact. The objective of this systematic review is to collate the world’s literature on early interventions aimed at preventing PTSD among survivors of critical illness.

Methods and analysis

We will perform a qualitative systematic review of human clinical trials of interventions aimed at preventing or reducing critical illness-related PTSD symptoms. We will methodically search CENTRAL, MEDLINE, Embase and CINAHL. We will also search websites containing details on clinical trials registration (National Library of Medicine’s ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform), as well as screen reference lists of the articles we select for inclusion to identify additional studies for potential inclusion. Two authors will independently review all search results. After identification and inclusion of articles, we will use a standardised form for data extraction. We will use tables to describe the study type, populations, interventions tested and timing of interventions, outcome measures and effects of interventions on outcome measures compared with control groups. This review will be completed between 1 August 2017 and 31 August 2017.

Ethics and dissemination

The proposed systematic review will not collect individual patient level data and does not require ethical approval. Results of this study will contribute to the understanding of critical illness-related PTSD and help prompt future research aimed at further developing interventions to prevent PTSD symptoms in survivors of critical illness.

PROSPERO registration number

This systematic review is registered in the PROSPERO international prospective register of systematic reviews (registration number CRD42017069672).
Feasibility and acceptability of a patient-reported outcome intervention in chronic heart failure
Authors: Kane Pauline M , Daveson Barbara A , Ryan Karen , Ellis-Smith Clare I , Mahon Niall G , McAdam Brendan , McQuilllan Regina , Tracey Cecelia , Howley Christine , O’Gara Geraldine , Raleigh Caroline , Higginson Irene J , Koffman Jonathan , Murtagh Fliss E M
Published: September 2017

Patients with chronic heart failure (CHF) have symptoms and concerns which are inadequately addressed. Patient-reported outcome measures (PROMs) can potentially improve the identification and management of advanced symptoms and palliative concerns. However, these have not been used in CHF.

Objectives

To examine the feasibility and acceptability of using a PROM—the Integrated Palliative care Outcome Scale (IPOS)—together with heart failure nurse education and training to improve the identification and management of symptoms and concerns among patients with CHF.

Methods

A parallel, mixed methods design with an embedded qualitative component was used to examine the feasibility of recruitment, retention, intervention adherence/compliance and follow-up assessment completion (symptom burden, quality of life, psychological well-being). Patient and nurse qualitative semistructured interviews explored intervention and study design feasibility and its acceptability.

Results

Conversion to consent was 46.9% (372 screened, 81 approached, 38 recruited). 66% of patient participants completed the IPOS; 6% of IPOS questionnaire items were missing (non-response). Over two-thirds (65.6%) of these missing items related to three patients. No item was consistently missing; appetite was the most frequent missing item (1.4%). 92% of participants who completed the IPOS completed all follow-up assessments (1–2 days, 1–2 weeks and 4–6 weeks post-IPOS completion) with no missing data. The a priori feasibility objectives were met. Patients and nurses reported the intervention and study design feasible and acceptable.

Conclusions

A palliative-specific PROM-based intervention is feasible and acceptable to both patients with CHF and nurses in nurse-led disease management clinics for the purposes of both clinical care and research.
Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease
Authors: Evangelista Arturo , Gallego Pastora , Calvo-Iglesias Francisco , Bermejo Javier , Robledo-Carmona Juan , Sánchez Violeta , Saura Daniel , Arnold Roman , Carro Amelia , Maldonado Giuliana , Sao-Avilés Augusto , Teixidó Gisela , Galian Laura , Rodríguez-Palomares José , García-Dorado David
Published: September 2017

Objective

Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications.

Methods

Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established.

Results

Three BAV morphotypes were identified: right–left coronary cusp fusion (RL) in 72.9%, right–non-coronary (RN) in 24.1% and left–non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN.

Conclusions

Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.
Impact of presynaptic sympathetic imbalance in long-QT syndrome by positron emission tomography
Authors: Zumhagen Sven , Vrachimis Alexis , Stegger Lars , Kies Peter , Wenning Christian , Ernsting Marko , Müller Jovanca , Seebohm Guiscard , Paul Matthias , Schäfers Klaus , Stallmeyer Birgit , Schäfers Michael , Schulze-Bahr Eric
Published: September 2017

Objective

We investigated the impact of cardiac presynaptic norepinephrine recycling in patients with long-QT syndrome (LQTS) using positron emission tomography (PET) with 11C-meta-hydroxyephedrine ([11C]mHED-PET).

Methods

[11C]mHED-PET was performed in 25 patients with LQTS (LQT1: n=14; LQT2: n=11) and 20 healthy controls and correlated with clinical parameters. [11C]mHED-PET images were analysed for global and regional retention indices (RI) and washout rates (WO) reflecting dynamic parameters of the tracer activity.

Results

Global and regional RI values were similar between patients with LQTS and controls. Although the global WO rates were similar between these groups, regional WO rates were on average higher in the lateral left ventricle (LV) wall in patients with LQTS (dose, mean ±SD; 0.08±0.14 vs 0.00%±0.09% min–1; p=0.033). In addition, patients with LQTS with a longer QTc interval showed a higher global WO rate. Clinical symptoms correlated with higher global WO rates. In the presence of normal global WO rates, asymptomatic LQTS patients showed higher global RI values.

Conclusion

The increased regional WO rate of [11C]mHED in the lateral LV suggests an imbalance of presynaptic catecholamine reuptake and release, resulting in a higher synaptic catecholamine concentration, in particular in LQT1 patients. This might enhance β-adrenoceptor signalling and thereby aggravate inherited ion channel dysfunction and may facilitate occurrence of ventricular tachyarrhythmias. Detection of regional differences in LV sympathetic nervous function may modify disease expression and potentially serve as a non-invasive risk marker in congenital LQTS.

Trial registration number

2006-002767-41;Results.
Trajectories and characteristics of work disability before and after acute myocardial infarction
Authors: Wang Mo , Vaez Marjan , Dorner Thomas Ernst , Tiihonen Jari , Voss Margaretha , Ivert Torbjörn , Mittendorfer-Rutz Ellenor
Published: September 2017

Objective

Scientific knowledge on work disability in terms of sickness absence and disability pension (SA/DP) among patients with acute myocardial infarction (AMI) is scarce. The study aimed to investigate trajectories of SA/DP among individuals with or without AMI and examined the associations between sociodemographic, morbidity and coronary revascularisation characteristics with such trajectories among patients with AMI.

Methods

This is a population-based cohort study of 10 255 individuals aged 30–60 years who had a first AMI during 2008–2010 and were alive 30 days after AMI. Each case was matched by sociodemographics to one control without AMI. Trajectories of annual SA/DP months over a 6-year period for cases and controls were analysed by group-based trajectory modelling. Associations of characteristics with trajectory groups were estimated by Χ2 test and multinomial logistic regression.

Results

The majority of patients (59%) had slightly increased annual levels of SA/DP (1 month) at the time of AMI, which returned to no SA/DP 2 years after the event. One group (4%) had increasing SA/DP months preceding and after AMI. Three groups showed constant SA/DP months on low (14%), medium (9%) and high (15%) levels. Sex, unemployment, education, musculoskeletal disorders and prescription of antidepressants were the strongest factors discriminating the SA/DP trajectories (R2difference=0.02–0.03, p<0.01).

Conclusions

The majority of patients with AMI have a good outcome in terms of low levels of work disability within 2 years after AMI. Patterns of SA/DP before AMI, sex, socioeconomic status as well as comorbid musculoskeletal and mental disorders provide crucial clinical information on work disability after AMI.
Ethanol metabolism by alcohol dehydrogenase or cytochrome P4502E1 differentially impairs hepatic protein trafficking and growth hormone signaling
Authors: Doody Erin E. , Groebner Jennifer L. , Walker Jetta R. , Frizol Brittnee M. , Tuma Dean J. , Fernandez David J. , Tuma Pamela L.
Published: September 2017

Impaired growth hormone-mediated signaling is observed in ethanol-exposed hepatocytes and is explained by differential effects of alcohol dehydrogenase (ADH)- and cytochrome P4502E1 (CYP2E1)-mediated ethanol metabolism on the Jak2/STAT5B pathway.
Krüppel-like factor 5 is essential for maintenance of barrier function in mouse colon
Authors: Liu Yang , Chidgey Martyn , Yang Vincent W. , Bialkowska Agnieszka B.
Published: September 2017

Krüppel-like factor 5 (KLF5) is a member of the zinc finger family of transcription factors that regulates homeostasis of the intestinal epithelium. Previous studies suggested an indispensable role of KLF5 in maintaining intestinal barrier function. In the current study, we investigated the mechanisms by which KLF5 regulates colonic barrier function in vivo and in vitro. We used an inducible and a constitutive intestine-specific Klf5 knockout mouse models ( Villin-CreERT2;Klf5fl/fldesignated as Klf5ΔINDand Villin-Cre;Klf5fl/flas Klf5ΔIS) and studied an inducible KLF5 knockdown in Caco-2 BBe cells using a lentiviral Tet-on system (Caco-2 BBe KLF5ΔIND). Specific knockout of Klf5 in colonic tissues, either inducible or constitutive, resulted in increased intestinal permeability. The phenotype was accompanied by a significant reduction in Dsg2, which encodes desmoglein-2, a desmosomal cadherin, at both mRNA and protein levels. Transmission electron microscopy showed alterations of desmosomal morphology in both KLF5 knockdown Caco-2 BBe cells and Klf5 knockout mouse colonic tissues. Inducible knockdown of KLF5 in Caco-2BBe cells grown on Transwell plates led to impaired barrier function as evidenced by decreased transepithelial electrical resistance and increased paracellular permeability to fluorescein isothiocyanate-4 kDa dextran. Furthermore, DSG2 was significantly decreased in KLF5 knockdown cells, and DSG2 overexpression partially rescued the impaired barrier function caused by KLF5 knockdown. Electron microscopy studies demonstrated altered desmosomal morphology after KLF5 knockdown. In combination with chromatin immunoprecipitation analysis and promoter study, our data show that KLF5 regulates intestinal barrier function by mediating the transcription of DSG2, a gene encoding a major component of desmosome structures.

NEW & NOTEWORTHY The study is original research on the direct function of a Krüppel-like factor on intestinal barrier function, which is commonly exerted by cell junctions, including tight junctions, adherens junctions, and desmosomes. Numerous previous studies were focused on tight junctions and adherens junctions. However, this study provided a new perspective on how the intestinal barrier function is regulated by KLF5 through DSG2, a component of desmosome complexes.
Application of DC-AC Hybrid Grid and Solar Photovoltaic Generation with Battery Storage Using Smart Grid
Authors: Rauf Shoaib , Khan Nasrullah
Published: September 2017

Smart grid for the past few years has been the prime focus of research in power systems. The aim is to eliminate load shedding and problematic blackout conditions, further offering cheap and continuous supply of electricity for both large and small consumers. Another benefit is to integrate renewable energy resources with existing dump grid in more efficient and cost-effective manner. In past few years, growing demand for sustainable energy increases the consumption of solar PV. Since generation from solar PV is in DC and most of the appliances at home could be operated on DC, AC-DC hybrid distribution system with energy management system is proposed in this paper. EMS helps to shift or control the auxiliary load and compel the users to operate specific load at certain time slots. These techniques further help to manage the excessive load during peak and off peak hours. It demonstrates the practical implementation of DC-AC network with integration of solar PV and battery storage with existing infrastructure. The results show a remarkable improvement using hybrid AC-DC framework in terms of reliability and efficiency. All this functioning together enhances the overall efficiency; hence, a secure, economical, reliable, and intelligent system leads to a smart grid.
Dual Inhibition of Hedgehog and c-Met Pathways for Pancreatic Cancer Treatment
Authors: Rucki Agnieszka A. , Xiao Qian , Muth Stephen , Chen Jianlin , Che Xu , Kleponis Jennifer , Sharma Rajni , Anders Robert A. , Jaffee Elizabeth M. , Zheng Lei
Published: September 2017

Pancreatic ductal adenocarcinoma (PDAC) is one of the most chemotherapy- and radiotherapy-resistant tumors. The c-Met and Hedgehog (Hh) pathways have been shown previously by our group to be key regulatory pathways in the primary tumor growth and metastases formation. Targeting both the HGF/c-Met and Hh pathways has shown promising results in preclinical studies; however, the benefits were not readily translated into clinical trials with PDAC patients. In this study, utilizing mouse models of PDAC, we showed that inhibition of either HGF/c-Met or Hh pathways sensitize the PDAC tumors to gemcitabine, resulting in decreased primary tumor volume as well as significant reduction of metastatic tumor burden. However, prolonged treatment of single HGF/c-Met or Hh inhibitor leads to resistance to these single inhibitors, likely because the single c-Met treatment leads to enhanced expression of Shh, and vice versa. Targeting both the HGF/c-Met and Hh pathways simultaneously overcame the resistance to the single-inhibitor treatment and led to a more potent antitumor effect in combination with the chemotherapy treatment. Mol Cancer Ther; 16(11); 2399–409. ©2017 AACR.
Inhibition of Discoidin Domain Receptor 1 Reduces Collagen-mediated Tumorigenicity in Pancreatic Ductal Adenocarcinoma
Authors: Aguilera Kristina Y. , Huang Huocong , Du Wenting , Hagopian Moriah M. , Wang Zhen , Hinz Stefan , Hwang Tae Hyun , Wang Huamin , Fleming Jason B. , Castrillon Diego H. , Ren Xiaomei , Ding Ke , Brekken Rolf A.
Published: September 2017

The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated protumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells. Pharmacologic inhibition of DDR1 with an ATP-competitive orally available small-molecule kinase inhibitor (7rh) abrogated collagen-induced DDR1 signaling in pancreatic tumor cells and consequently reduced colony formation and migration. Furthermore, the inhibition of DDR1 with 7rh showed striking efficacy in combination with chemotherapy in orthotopic xenografts and autochthonous pancreatic tumors where it significantly reduced DDR1 activation and downstream signaling, reduced primary tumor burden, and improved chemoresponse. These data demonstrate that targeting collagen signaling in conjunction with conventional cytotoxic chemotherapy has the potential to improve outcome for pancreatic cancer patients. Mol Cancer Ther; 16(11); 2473–85. ©2017 AACR.
mTOR Kinase Inhibition Effectively Decreases Progression of a Subset of Neuroendocrine Tumors that Progress on Rapalog Therapy and Delays Cardiac Impairment
Authors: Orr-Asman Melissa A. , Chu Zhengtao , Jiang Min , Worley Mariah , LaSance Kathleen , Koch Sheryl E. , Carreira Vinicius S. , Dahche Hanan M. , Plas David R. , Komurov Kakajan , Qi Xiaoyang , Mercer Carol A. , Anthony Lowell B. , Rubinstein Jack , Thomas Hala E.
Published: September 2017

Inhibition of mTOR signaling using the rapalog everolimus is an FDA-approved targeted therapy for patients with lung and gastroenteropancreatic neuroendocrine tumors (NET). However, patients eventually progress on treatment, highlighting the need for additional therapies. We focused on pancreatic NETs (pNET) and reasoned that treatment of these tumors upon progression on rapalog therapy, with an mTOR kinase inhibitor (mTORKi), such as CC-223, could overcome a number of resistance mechanisms in tumors and delay cardiac carcinoid disease. We performed preclinical studies using human pNET cells in vitro and injected them subcutaneously or orthotopically to determine tumor progression and cardiac function in mice treated with either rapamycin alone or switched to CC-223 upon progression. Detailed signaling and RNA sequencing analyses were performed on tumors that were sensitive or progressed on mTOR treatment. Approximately 57% of mice bearing pNET tumors that progressed on rapalog therapy showed a significant decrease in tumor volume upon a switch to CC-223. Moreover, mice treated with an mTORKi exhibited decreased cardiac dilation and thickening of heart valves than those treated with placebo or rapamycin alone. In conclusion, in the majority of pNETs that progress on rapalogs, it is possible to reduce disease progression using an mTORKi, such as CC-223. Moreover, CC-223 had an additional transient cardiac benefit on valvular fibrosis compared with placebo- or rapalog-treated mice. These results provide the preclinical rationale to further develop mTORKi clinically upon progression on rapalog therapy and to further test their long-term cardioprotective benefit in those NET patients prone to carcinoid syndrome. Mol Cancer Ther; 16(11); 2432–41. ©2017 AACR.
A CRISPR/Cas9–Based Screening for Non-Homologous End Joining Inhibitors Reveals Ouabain and Penfluridol as Radiosensitizers
Authors: Du Jie , Shang Jun , Chen Fei , Zhang Yushuo , Yin Narui , Xie Ting , Zhang Haowen , Yu Jiahua , Liu Fenju
Published: September 2017

Non-homologous end joining (NHEJ) is the major pathway responsible for the repair of ionizing radiation (IR)–induced DNA double-strand breaks (DSB), and correspondingly regulates the cellular response to IR. Identification of NHEJ inhibitors could substantially enhance the tumor radiosensitivity and improve the therapeutic efficiency of radiotherapy. In this study, we demonstrated a screening for NHEJ inhibitors using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and high-resolution melting (HRM) analysis. Because NHEJ is regarded as an error-prone mechanism, the NHEJ-mediated ligation of the site-specific DSB induced by Cas9 nuclease would eventually cause the mutation of the targeted sequence. Then, HRM analysis, a reliable and rapid assay for detecting sequence variation, was performed to evaluate the mutation efficiency of the targeted site. Validating analysis confirmed the NHEJ activities were positively correlated with the mutation frequencies. Next, an approved drug library containing 1,540 compounds was interrogated by using this screening strategy. Our results identified ouabain, a cardiotonic agent, and penfluridol, an antipsychotic agent, have the capacity to restrain NHEJ activity. Further experiments in vitro revealed the radiosensitizing effects of these compounds. Overall, we presented a cell-based screening for NHEJ inhibitors, which could promote the discovery of novel radiosensitizers. Mol Cancer Ther; 17(2); 419–31. ©2017 AACR.

See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”
Recurrent Tumor Cell–Intrinsic and –Extrinsic Alterations during MAPKi-Induced Melanoma Regression and Early Adaptation
Authors: Song Chunying , Piva Marco , Sun Lu , Hong Aayoung , Moriceau Gatien , Kong Xiangju , Zhang Hong , Lomeli Shirley , Qian Jin , Yu Clarissa C. , Damoiseaux Robert , Kelley Mark C. , Dahlman Kimberley B. , Scumpia Philip O. , Sosman Jeffrey A. , Johnson Douglas B. , Ribas Antoni , Hugo Willy , Lo Roger S.
Published: September 2017

Treatment of advanced BRAFV600-mutant melanoma using a BRAF inhibitor or its combination with a MEK inhibitor typically elicits partial responses. We compared the transcriptomes of patient-derived tumors regressing on MAPK inhibitor (MAPKi) therapy against MAPKi-induced temporal transcriptomic states in human melanoma cell lines or murine melanoma in immune-competent mice. Despite heterogeneous dynamics of clinical tumor regression, residual tumors displayed highly recurrent transcriptomic alterations and enriched processes, which were also observed in MAPKi-selected cell lines (implying tumor cell–intrinsic reprogramming) or in bulk mouse tumors (and the CD45-negative or CD45-positive fractions, implying tumor cell–intrinsic or stromal/immune alterations, respectively). Tumor cell–intrinsic reprogramming attenuated MAPK dependency, while enhancing mesenchymal, angiogenic, and IFN-inflammatory features and growth/survival dependence on multi-RTKs and PD-L2. In the immune compartment, PD-L2 upregulation in CD11c+ immunocytes drove the loss of T-cell inflammation and promoted BRAFi resistance. Thus, residual melanoma early on MAPKi therapy already displays potentially exploitable adaptive transcriptomic, epigenomic, immune-regulomic alterations.

Significance: Incomplete MAPKi-induced melanoma regression results in transcriptome/methylome-wide reprogramming and MAPK-redundant escape. Although regressing/residual melanoma is highly T cell–inflamed, stromal adaptations, many of which are tumor cell–driven, could suppress/eliminate intratumoral T cells, reversing tumor regression. This catalog of recurrent alterations helps identify adaptations such as PD-L2 operative tumor cell intrinsically and/or extrinsically early on therapy. Cancer Discov; 7(11); 1248–65. ©2017 AACR.

See related commentary by Haq, p. 1216.

This article is highlighted in the In This Issue feature, p. 1201
Predictive Value of Computed Tomography Angiography–Determined Occlusion Type in Stent Retriever Thrombectomy
Authors: Baek Jang-Hyun , Kim Byung Moon , Yoo Joonsang , Nam Hyo Suk , Kim Young Dae , Kim Dong Joon , Heo Ji Hoe , Bang Oh Young
Published: September 2017

Background and Purpose—

We investigated whether occlusion type identified with computed tomography angiography (CTA-determined occlusion type) could predict endovascular treatment success using stent retriever (SR) thrombectomy.

Methods—

Consecutive patients with stroke who underwent CTA and then endovascular treatment for intracranial large artery occlusion were retrospectively reviewed. CTA-determined occlusion type was classified into truncal-type occlusion or branching-site occlusion and compared with digital subtraction angiography–determined occlusion type during endovascular treatment. Three rapidly- and readily-assessable pre-procedural findings (CTA-determined occlusion type, atrial fibrillation, and hyperdense artery sign), which may infer occlusion pathomechanism (embolic versus nonembolic) before endovascular treatment, were evaluated for association with SR success along with stroke risk factors and laboratory results. In addition, the predictive power of the 3 pre-procedural findings for SR success was compared with receiver operating characteristic curve analyses.

Results—

A total of 238 patients (mean age, 70.0 years; male patients, 52.9%) were included in this study. CTA-determined occlusion type corresponded adequately with digital subtraction angiography–determined occlusion type (
P
=0.453). Atrial fibrillation (odds ratio, 2.66; 95% confidence interval, 1.25–5.66) and CTA-determined branching-site occlusion (odds ratio, 8.20; confidence interval, 3.45–19.5) were independent predictors for SR success. For predicting SR success, the area under the receiver operating characteristic curve value for CTA-determined branching-site occlusion (0.695) was significantly greater than atrial fibrillation (0.594;
P
=0.038) and hyperdense artery sign (0.603;
P
=0.023).

Conclusions—

CTA-determined branching-site occlusion was significantly associated with SR success. Furthermore, among the 3 rapidly- and readily-assessable pre-procedural findings, CTA-determined branching-site occlusion had the greatest predictive power for SR success.
The Expression of Religious Beliefs: In the Name of Pluralism, although Not Quite Religious
Authors: Callamard Agnés
Published: September 2017

The 25 years’ jurisprudence of the European Court of Human Rights on the intersection between expression and religion reveals that three main ideas of religion have coexisted alongside each other, for many decades predating the current era. The jurisprudence also shows that the Court somehow accommodated (and justified) these different ideas through a focus on democratic pluralism (not religious pluralism), a conception of pluralism which makes religion (including in its diverse expressions) subservient to democratic principles.
Limitations on Freedom of Religion and Belief in the Jurisprudence of the European Court of Human Rights in the Quarter Century since Its Judgment in Kokkinakis v. Greece
Authors: Hill Mark , Barnes Katherine
Published: September 2017

The manifestation of religious beliefs under Article 9 the European Convention on Human Rights is not absolute but may be subject to prescribed limitations. This article discusses the nature and extent of those limitations, as interpreted in the case law of the European Court of Human Rights from its decision in Kokkinakis v. Greece up to the present. It contrasts the prescriptive text of the Article with its lose and inconsistent interpretation by the Court in Strasbourg. Particular attention is given to the criteria of “prescribed by law”, “necessary in a democratic society”, “public safety”, “public order, health or morals” and “the rights and freedoms of others”. It seeks to divine principles from the varied jurisprudence, particularly at its intersection with the Court’s illusory doctrine of margin of appreciation.
A Typology of Dissent in Religion Cases in the Grand Chamber of the European Court of Human Rights
Authors: van Bijsterveld Sophie
Published: September 2017

Dissenting opinions in European Court of Human Rights judgments are a familiar phenomenon. Nevertheless, they receive little or no systematic attention. This essay presents a typology of dissenting opinions in religion cases in the Grand Chamber of the European Court. It identifies patterns of dividing lines within Grand Chamber decisions in religion cases and discusses these patterns.
Soluble Endoglin (CD105) Serum Level as a Potential Marker in the Management of Head and Neck Paragangliomas
Authors: Litwiniuk Małgorzata , Niemczyk Kazimierz , Niderla-Bielińska Justyna , Łukawska-Popieluch Izabela , Grzela Tomasz
Published: September 2017

Objectives:

To assess the expression of endoglin in head and neck paragangliomas and the soluble endoglin level in serum of paraganglioma patients.

Methods:

Seven tumor samples of patients operated for cervical paraganglioma were assessed, as well as serum samples collected preoperatively, on days 4 and 28 postoperation. Serum level of endoglin in healthy controls was also determined. Tumor samples were subjected to immunofluorescent staining and examined with confocal microscope. The level of soluble endoglin in serum samples was examined using the immunoenzymatic assay (ELISA).

Results:

Endoglin was highly expressed in all tumor samples. The level of soluble endoglin was significantly higher in paraganglioma patients compared to healthy controls and correlated with the tumor size. The serum level of s-endoglin was reduced after surgical excision of the tumor and remained stable after 4 weeks in all patients with complete resection of the tumor.

Conclusion:

Endoglin is an important factor in the pathophysiology of head and neck paragangliomas and may be a potential diagnostic and prognostic marker in these types of tumors.
The Distinction of Fields
Authors: Mitnick Barry M.
Published: September 2017

The concept of scientific field lacks a definition in a form allowing the distinction of whether a particular academic area of study is or is not a true scientific field. Starting with the classic definition by Whitley of a field as a “reputational work organization,” this essay extracts eleven explicit and implied features of a field from Whitley’s definition and discussion, extending his analysis. The article reviews Hambrick and Chen’s model of field formation as an “admittance-seeking social movement.” Hambrick and Chen argue that strategic management followed that model with success, offering the SIM Division of the Academy of Management as an unsuccessful example. The article notes errors in their assessment of SIM, argues that Hambrick and Chen are really offering a model of what I term condensation and promulgation of a field and that their model cannot be used to determine whether a field exists. The article applies the extended Whitley model of a field to examine three candidate fields within SIM: corporate social responsibility (CSR)/corporate social performance (CSP), stakeholder theory, and corporate political activity (CPA). I conclude that none is technically a field, and considering as well the comments of three senior scholars who contributed to the symposium, the article discusses the potential trajectory of fields in SIM.
Home and School Environmental Influences on Adolescents’ Sociopolitical Group Participation: Implications for Increasing Youth Involvement
Authors: Curtis Christopher A.
Published: September 2017

The potential benefits associated with sociopolitical group involvement for participating youth have been well documented in the existing literature. Yet, little is known about what motivates voluntary participation in such programs among youth. The purpose of this study is to explore what environmental factors influence youth civic engagement through participation in sociopolitical groups (e.g., service-learning or community service programs). To do this, several independent variables captured in The Commission on Youth Voting and Civic Knowledge Youth Post Election Survey 2012 dataset and the respondents’ reported participation in social or political groups while in high school were observed. Binary and ordinal logistic regression modeling were used to analyze the data. The results indicate that several factors in the home and school environment are related to an increased probability of youth joining a sociopolitical group at school, away from school, or both. These findings suggest that the messages crafted to encourage youth participation in sociopolitical groups should account for the demographic (i.e., racial, gender, and cultural) and experiential (i.e., civics education quality) differences present within the target population.
A pilot study of flipped cardiopulmonary resuscitation training: Which items can be self-trained?
Authors: Van Raemdonck Veerle , Aerenhouts Dirk , Monsieurs Koen , De Martelaer Kristine
Published: September 2017

Objective:

This study evaluated self-trained basic life support (BLS) skills acquired from an e-learning platform to design a complementary in-class training approach.

Design:

In total, 41 students (15–17 years, 29 men) participated in a pilot study on self-training in BLS. After 6 weeks, a compression-only cardiopulmonary resuscitation (CPR) test assessed the skills acquired.

Setting:

A practice-based research setting. All data were collected in Flemish secondary schools in the context of the regular school curriculum.

Methods:

All tests were video-recorded. Data on motor skills were additionally collected on a Resusci Anne mannequin with Skillreporting software®. Quantitative data were analysed by analysis of variance (ANOVA). The qualitative aspects of basic life-saving actions were evaluated using European Resuscitation Council (ERC) guidelines.

Results:

Alerting emergency services, checking for consciousness and placing electrodes can be learned autonomously and be taught by means of pre-instruction. Hands-on training is necessary for compression skills and freeing the airway.

Conclusion:

Self-training in BLS offers insight into a flipped classroom CPR training strategy. Hands-on training should focus on motor skills, including head tilt and compression depth.
Examining the Predictors of Parole Release in a Rural Jail Population
Authors: Bowman Edward L. , Ely Katherine
Published: September 2017

Parole is the linchpin of correctional practices, but few studies have examined discretionary parole in a rural population. The current study examines static risk and dynamic needs that influence parole decision making in a rural jail population. Data were collected on parole releases over a 3-year period beginning in 2012. Offenders received recommendations for parole from a reentry assessment team. Logistic regression was used to explain variance in the factors influencing discretionary parole release. Obstacles or challenges that offenders face when paroling to a rural location were also examined. Several policy recommendations are addressed.
Vitality, Language Use, and Life Satisfaction: A Study of Bilingual Hungarian Adolescents Living in Romania
Authors: Dragojevic Marko , Gasiorek Jessica , Vincze László
Published: September 2017

This study examined the relationship between objective and subjective vitality, in-group language use, and life satisfaction among two groups of bilingual Hungarians adolescents living in Romania: a low objective vitality group from Cluj-Napoca/Kolozsvár, where Hungarians are the demographic minority, and a high objective vitality group from Sfântu Gheorghe/Sepsiszentgyörgy, where Hungarians are the demographic majority. Consistent with predictions, the high objective vitality group reported higher subjective Hungarian vitality, lower subjective Romanian vitality, more frequent use of the Hungarian language, and higher life satisfaction, compared with the low objective vitality group. The effects of objective vitality on language use were partially mediated by subjective Romanian (but not Hungarian) vitality. Conversely, the effects of objective vitality on life satisfaction were fully mediated by subjective Hungarian (but not Romanian) vitality.
Beyond Color-blindness: (Re) Theorizing Racial Ideology
Authors: Doane Ashley (“Woody”)
Published: September 2017

The study of color-blind racial ideology has made a significant contribution to the understanding of contemporary racism through its elaboration of the dominant racial ideology—a worldview grounded in the claim that race no longer “matters” as an obstacle to success in a “postracial” United States. Despite, or perhaps as a result of this success, the study of color-blind racial ideology has in many ways become stagnant. Following a critique of the current state of theorizing color-blindness, I strive to lay the foundation for a broader framework for understanding racial ideology. In this article, I undertake three core tasks: first, to present a general framework for understanding racial ideologies as fluid and dynamic constructions that are linked to a racial system; second, to outline how color-blind racial ideology is evolving and adapting in response to political challenges and changing social conditions; and finally, to discuss challenges to the hegemony of color-blindness and to propose an agenda for research on the future direction of racial ideology.
Is Blindness Contagious? Examining Racial Attitudes among People of Color with Close Interracial Relationships
Authors: Gonlin Vanessa , Campbell Mary E.
Published: September 2017

Are people of color with close relationships with whites more likely to embrace colorblind racial ideologies (CBRI)? Using restricted data from waves 1 and 2 of the Portraits of American Life Study ( N = 2,713), collected in 2006 and 2012, we test whether black, Latina/o, and Asian respondents are more likely to express colorblind racial attitudes if they have an intimate partner or close friends who are white. We use ordinal logit models to examine seven CBRI attitudinal items, controlling for the respondent’s socioeconomic characteristics, immigrant generation, national origin, gender, age, characteristics of the city, and region. Although black, Latina/o, and Asian respondents are less likely to express CBRI than whites are, respondents of color with close relationships with whites are more likely to minimize certain types of racism, even after controlling for other characteristics of the individual. We discuss the implications of these findings, considering the patterns of antiblack and anti-immigrant attitudes among groups of color and placing them in the context of the more negative attitudes often expressed by whites. We also describe how other demographic patterns in these attitudes could shape future trends in attitudes and suggest possible interventions.
Restricting Back Pain and Subsequent Disability in Activities of Daily Living Among Community-Living Older Adults
Authors: Makris Una E. , Weinreich Mark A. , Fraenkel Liana , Han Ling , Leo-Summers Linda , Gill Thomas M.
Published: September 2017

Objective: To evaluate the relationship between back pain severe enough to restrict activity (restricting back pain) and subsequent disability in essential (e) and instrumental (i) activities of daily living (ADL) among community-living older adults. Method: In this prospective cohort study, we evaluated 754 adults, aged ≥70 years who were initially nondisabled in eADL. Restricting back pain and disability were assessed during monthly interviews for up to 159 months. Associations between restricting back pain and subsequent eADL and iADL disability were evaluated using recurrent events Cox models, adjusted for fixed-in-time and time-varying covariates. Results: Strong associations were found between restricting back pain and eADL and iADL disability, with hazard ratios (95% confidence intervals) of 3.47 [3.01, 3.90] and 2.33 [2.08, 2.61], respectively. Discussion: Restricting back pain was independently associated with subsequent disability in eADL and iADL. Interventions focused on decreasing restricting back pain in older adults may have the potential to reduce the subsequent burden of disability.
Flexor Digitorum Longus (FDL) or Flexor Hallucis Longus (FHL) Harvesting: Technical Tip and Case Studies
Authors: Lehnert Bruce , Nyska Meir , Ip Wing , Huynh Em , Palmanovich Ezequiel
Published: September 2017

Background:

Harvesting of the flexor digitorum longus (FDL) or the flexor hallucis longus (FHL) is a procedure used when tendon transfer is needed. It is commonly used in tibialis posterior reconstruction and Achilles tendon reconstruction. Harvesting of these tendons is sometimes difficult and time-consuming. It is important to obtain sufficient length to make a loop around the navicular bone or anchor it in the calcaneus. We describe a technique in which a loop is passed from proximal identification of the FDL or FHL through the tendon sheath, harvesting it from a minimal plantar approach.

Methods:

After using this technique, we evaluated 10 consecutive patients for neurovascular damage.

Results:

We found no postoperative neurovascular injuries.

Conclusions:

The technique described enables the surgeon to find the FDL/FHL tendon through the medial approach and obtain sufficient length for the procedure by cutting the distal portion of the tendon through an additional plantar incision. Our technical tip for passing the loop facilitates harvest of the tendon easily and safely using the plantar approach.

Level of Evidence:

IV, case series.
Rate of Neurologic Injury Following Lateralizing Calcaneal Osteotomy Performed Through a Medial Approach
Authors: Jaffe David , Vier David , Kane Justin , Kozanek Michal , Royer Christian
Published: September 2017

Background:

Calcaneal osteotomies are commonly used to correct varus hindfoot alignment in patients with symptomatic cavovarus deformity. Translational, closing wedge, and Malerba-type osteotomies have been implicated in the development of tarsal tunnel syndrome and neurologic injury to branches of the tibial nerve. The authors hypothesized that there would be minimal clinically important injury to the tibial nerve by performing a translational calcaneal osteotomy from a medial approach.

Methods:

All patients undergoing a cavovarus reconstruction by a single surgeon were identified. Patients were included if they underwent a lateralizing calcaneal osteotomy via medial approach. Demographics, operative reports, and clinic notes were reviewed to identify concomitant procedures performed, incidence of postoperative tarsal tunnel syndrome, complications, and preoperative and postoperative nerve examinations. Postoperative radiographs were reviewed for location of the osteotomy relative to the posterior tubercle.

Results:

Twenty-four patients underwent lateralizing calcaneal osteotomy via a medial approach. Of the osteotomies, 83.3% (20/24) were in the middle third of the calcaneus, with a mean of 11.6-mm translation. No patients developed postoperative tarsal tunnel syndrome or tibial nerve palsy.

Conclusion:

Lateralizing calcaneal osteotomy performed via a medial approach had a clinically negligible incidence of neurologic injury. Adequate translation was achieved to obtain correction of varus hindfoot deformity. The authors believe that there is less direct and less percussive injury to branches of the tibial nerve when performing the osteotomy from medial to lateral. This technique may represent an operative strategy to minimize risk to the tibial nerve and reduce neurologic deficit following cavovarus reconstruction.

Level of Evidence:

Level IV, case series.