bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of care for synchronous rectal cancer with liver-only metastasis: Results from the South Australian registry of metastatic colorectal cancer.
Authors: Roy Amitesh Chandra , Karapetis Christos Stelios , Piantadosi Cynthia , Townsend Amanda Rose , Padbury Rob , Carruthers Scott , Maddern Guy , Roder David , Moore James , Price Timothy Jay
Published: March 2017

701

Background: Management of rectal cancer with synchronous liver metastasis is not clear. Optimal timing of radiotherapy, chemotherapy, resection of primary and liver metastasis is debated. Methods: The South Australian Registry for metastatic colorectal cancer has entered all patients with mCRC since 1st February 2006. Registry data were analyzed to assess patient characteristics, therapy received and outcomes for patients with liver only metastasis and synchronous rectal or colon primary. KM analysis was used for survival outcomes. Results: 2677 patents had synchronous mCRC. 42% (n = 1125) had liver only metastasis (primary: 275 rectal/850 colon). The main differences between rectal/liver vs. colon/liver were: more males (68.7% v 57.8%, p = 0.001), younger age (65.8 v 73.3 years, p < 0.001) and less poorly differentiated histology (14.2% v 24.1%, p = 0.003). The rate of no surgery on the primary was 21.4% for rectal cancers v. 36% for colon (p ≤ 0.001). Liver surgery rates in both groups was similar (28.4% v 23.0% (p = 0.075). Out of the 275 rectal cancer patients, 100 (36.3%) had rectal surgery, 83 (30%) had chemo-RT and 47 (17%) had chemotherapy +/- targeted therapy as initial treatment, 45 (16%) patients had no treatment. Median OS of rectal cancer patients based on their initial treatment was 33.2m (Chemo-RT) vs. 22.2m (surgery) vs. 19.2m (chemotherapy +/- targeted therapy, p < 0.001). The mOS for rectal group was 22.8m v. 14.8m (p = 0.001) for colon group. For patients who had liver surgery mOS was 60.7m vs. 67.1m respectively. Survival was better if primary was rectum or left colon vs. right colon (mOS 18.3m vs 18.8m vs 10.2m respectively p < 0.001). Resection of the primary occurred first in all patients who had liver resection. Conclusions: Patients with synchronous rectal cancer with liver only metastases have better survival compared to those with colon cancer and liver only metastases. Where surgery is possible, OS is equivalent between the two groups and in our registry population surgery on the rectal primary or chemo-RT were found to be the preferred initial treatment for rectal cancer patients with synchronous liver metastases.
Cetuximab (CTX) in first-line treatment of elderly patients with metastatic colorectal cancer (mCRC), KRAS wild type: French multicentre prospective community-based registry and results.
Authors: Mineur Laurent , François Eric , Phelip Jean Marc , Guimbaud Rosine , Plassot Carine , Smith Denis Michel , Miglianico Laurent
Published: March 2017

760

Background: Pts included in clinical trials represent the unusual population in mCRC. This study aims to provide oncologist with a better understanding of the potential benefit of CT with CTX in older patients with mCRC KRAS wild type and evaluate prognostic variables on the PFS including the age. Methods: Premium cancer study is a French multicentre prospective community-based registry. 493 pts enrolled and 487 included between September 2009 to March 2012 from 94 French centers and physicians. Pts had to provide written informed consent and protocol submitted to regulatory authorities. Predefined efficacy endpoints was PFS. CTX was administrated at 250 mg/m2 weekly (n=100; 20.3%) or 500 mg/m2 every 2 weeks (n=380;77,2%), other n=13; 2.5%) CT regimen choice was at physician’s discretion.. The main analysis is PFS as well as analysis of prognostic factors of this PFS (29 items including age (< 65 years n=229; 65-74 years n= 165.; ≥75years n=93). Univariate analysis was performed for each covariate, PFS was estimated by Kaplan-Meier curves and compared by log-rank test. univariable Cox regression analysis was used to assess the association between each variable and outcome. Multivariable stepwise Cox models were then fitted for final variable selection of prognostic factors on PFS. Results: Univariate significant prognostic factors for PFS are OMS (0-1 vs 2-3), Tobacco, Site of tumor (right vs other), Number of metastatic organ (1 vs 2-3), Resecability of metastatic disease defined before CT (definitively non resectable metastases vs possible resectable), Surgery of mCRC, folliculitis or xerosis or paronychia grade 0-1 vs 2-4. Age was unidentified as a prognostic factor in univariate analysis. Four factors were independently associated with a better PFS: xerosis [hazard ratio (HR0,651); 95% confidence interval (CI) 0,494-0,857], (WHO PS) 0–1 (HR0,519 ; 95% CI 0,371–0,726) and folliculitis (HR 0,711; 95% CI0,558–0,956) metastases surgery 0,287(CI 0,205-0,403). Conclusions: CTX in combination with standard CT is effective, age is not identified as a prognostic factor for the PFS. Both groups of pts based on age benefit from CTX.
Free and bound plasmin in esophageal tumors and surrounding tissues in men and women.
Authors: Kit Oleg Ivanovich , Frantsiyants Elena Mikhaylovna , Kozlova Larisa , Pogorelova Yulia A. , Chugunova Natalya , Kolesnikov Evgeniy N. , Averkin Michail , Sanamyants Sergey V.
Published: March 2017

84

Background: Esophageal squamous cell carcinoma (ESCC) is 2 to 8 times more frequent in men than in women. Tumor progression is directly connected with plasmin participation in destruction of the extracellular matrix and the basement membrane surrounding tumor. The purpose of the study was a comparative analysis of plasminogen (PG), free plasmin (P) and plasmin bound in complex with α2-antiplasmin (PAP) in ESCC tissues of men (M) and women (W). Methods: ESCC tumor tissue (T) and its perifocal zone (PZ) were studied by the ELISA (19 men and 8 menopausal women aged 58-72, st II, G2, T2-3N0-1M0-1). The results were compared to the histologically unchanged tissue from the resection line (RL). PG, P and PAP were measured in 10% homogenates prepared in sterile saline, with recalculation per 1 g wet tissue). Data were processed using Statistica 10. Results: PG content in RL was 1.5 times higher in M than in W. PG in T of M was decreased by 2 times, in W by 3.3 times, in PZ of M – by 2.9 times, in W – by 2.3 times. PG in T and PZ of M was 2.5 and 1.2 times higher than in W. P content in RL of all patients was significantly lower than in other samples, but 1.4 times higher in M than in W. P in T and PZ of M was 3 and 2.5 times higher than in RL, in T and PZ of W – 3.5 and 2.8 times higher than in RL. Significant differences were observed between P levels in T (but not in PZ): 1.3 times higher in M than in W. PAP content was relatively constant in all tissues, with a slight prevalence in T and PZ of W. P/PAP ratio was elevated in all tissues compared to RL, but in T and PZ of M it was 1.4 and 1.2 times higher than in W. P/PAP in RL of M was 1.4 times higher than in W. Conclusions: The results show a higher aggressiveness of P in PZ and T of M, while P formation in T of W was less active. We reported on a higher content of PG activators in T and PZ of M, and taking into account the morbidity statistics and literature data we suppose the effect of androgens on the conditions of PG activation into P and manifestation of its biological features. P in PZ of both M and W can contribute in the expansion of a “tumor field”. P binding in PAP complex was similar in all studied tissues.
Combining pembrolizumab and palliative radiotherapy in gastroesophageal cancer to enhance anti-tumor T-cell response and augment the abscopal effect.
Authors: Chao Joseph , Chen Yi-Jen , Frankel Paul Henry , Chung Vincent M. , Lim Dean , Li Daneng , Fakih Marwan , Lee Peter P.
Published: March 2017

TPS220

Background: Pembrolizumab has demonstrated encouraging preliminary evidence of activity in small cohorts of gastroesophageal cancer patients (pts) when selected for tumor PD-L1 overexpression. Strategies should be further developed to enhance the potency of PD-1 inhibitors, even in pts whose tumors are not considered to have detectable PD-L1 expression. The abscopal effect is a rarely observed though well annotated clinical phenomenon in cancer radiotherapy (RT), in which non-irradiated metastatic lesions are noted to regress after radiation to the primary tumor site. In preclinical models, this phenomenon has been attributed to immune-mediated effects, while RT has been observed to increase tumor PD-L1 expression. This lends credence to ongoing efforts to combine RT and immune checkpoint inhibition. We present the study design for a phase II trial combining pembrolizumab and palliative RT in metastatic gastroesophageal squamous cell and adenocarcinoma pts. Methods: A target accrual of 14 pts will be assigned to palliative RT of 30 Gy over 10 fractions for symptoms from their primary tumor or a single target metastatic site in combination with fixed dose pembrolizumab 200 mg every 3 weeks. Symptomatic brain metastases will be excluded. Pembrolizumab will be continued until disease progression, intolerable toxicity, or 35 administrations (~2 years). Pts will be required to undergo sequential biopsies of a non-target metastatic site (inclusive of malignant ascites) with timepoints occurring pre-treatment and ~21 days after completion of RT. Biomarkers of immune response and overall response rate (RECIST1.1, irRECIST) will be a composite primary endpoint; progression-free and overall survival, and toxicities will be secondary endpoints. Quantitative spatial image analyses of biopsy samples will be performed to examine changes in tumor cell-stromal interactions inclusive of CD4, CD8, Treg, and MDSC populations as well as tumor PD-L1/PD-1 expression levels. The results will assist in determining mechanisms of response and resistance to combination RT and PD-1 targeting strategies. Clinical trial information: NCT02830594.
SWOG S1505: A randomized phase II study of perioperative mFOLFIRINOX vs. gemcitabine/nab-paclitaxel as therapy for resectable pancreatic adenocarcinom.
Authors: Sohal Davendra , McDonough Shannon L , Ahmad Syed A. , Gandhi Namita , Beg Muhammad Shaalan , Wang-Gillam Andrea , Guthrie Katherine A , Lowy Andrew M. , Philip Philip Agop , Hochster Howard S.
Published: March 2017

TPS508

Background: Clinical outcomes after curative therapy for resectable pancreatic ductal adenocarcinoma (PDA) remain suboptimal. Series show that 70-85% of patients die of systemic recurrence. Improved overall survival (OS) in the metastatic setting with the use of multi-agent chemotherapy regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel) holds the promise of progress in the curative setting as well. However, aggressive systemic therapy is usually not feasible after major pancreatic surgery. Therefore, early control of systemic disease by increased preoperative chemotherapy may improve outcomes. Furthermore, the perioperative platform facilitates early identification of patients with chemotherapy-resistant tumors and allows prospective biomarker studies in the future. Methods: This is a randomized phase II study intended to choose the most promising perioperative regimen to test in a larger trial. Eligibility requirements include patients with an ECOG PS of 0 or 1, a confirmed histopathologic diagnosis of PDA, and resectable disease as confirmed by central radiology review: no involvement of the celiac, common hepatic, or superior mesenteric arteries (and, if present, variants); no involvement, or < 180° interface between tumor and vessel wall, of the portal or superior mesenteric veins; patent portal vein/splenic vein confluence; no metastases. Treatment includes 12 weeks [either mFOLFIRINOX (5-fluorouracil infusion (no bolus), irinotecan, oxaliplatin), or gemcitabine/nab-paclitaxel] of preoperative chemotherapy, followed by surgical resection and 12 weeks of identical postoperative chemotherapy. Primary outcome is 2-year OS, using a “pick the winner” design with minimum activity requirements. Assuming a historical 2-year OS of 40% and a 58% alternative hypothesis, 88% power, a 1-sided α of 0.05, and 100 eligible patients, the design provides a 90% probability of selecting the better regimen. The study opened through the National Clinical Trials Network (NCT02562716), and is supported by NIH/NCI/NCTN grants CA180888, CA180819, CA180821, CA180833. Clinical trial information: NCT02562716.
Gemcitabine and cisplatin plus ramucirumab or merestinib or placebo in first-line treatment for advanced or metastatic biliary tract cancer: A double-blind, randomized phase II trial.
Authors: Sama Ashwin Reddy , Denlinger Crystal Shereen , Vogel Arndt , He Aiwu Ruth , Bousmans Nathalie , Zhang Wei , Walgren Richard A. , Valle Juan W.
Published: March 2017

TPS509

Background: Angiogenesis and aberrant MET signaling are implicated in the pathogenesis and progression of invasive biliary tract cancers (BTC), including adenocarcinomas of the gallbladder, intra- and extra-hepatic bile ducts, and ampulla of Vater. JSBF (NCT02711553) is a phase II, multicenter, randomized, and double-blinded study, designed to evaluate the efficacy and safety of standard of care (SOC) gemcitabine and cisplatin in combination with either ramucirumab (human IgG1 VEGFR2 monoclonal antibody) or merestinib (oral type II MET kinase inhibitor) or respective placebo for the first-line treatment of advanced or metastatic BTC. Methods: Eligible patients with advanced or metastatic BTC will be randomized to oral merestinib 80 mg, oral placebo, intravenous (IV) ramucirumab 8mg/kg, or IV placebo, in a 2:1:2:1 fashion. Randomization will be stratified by primary tumor site, presence of metastases, and geographic region. In addition to the randomly assigned treatment, all patients will receive SOC first-line treatment with up to 8 cycles of IV gemcitabine 1000mg/m2 + cisplatin 25mg/m2 on days 1 and 8 of 21-day cycles. IV ramucirumab and placebo will be given on days 1 and 8 of each cycle; oral treatments will be taken daily. Investigational treatment or placebo may continue past 8 cycles until disease progression or a criterion for discontinuation is met. The primary endpoint is progression-free survival, by intention-to-treat analysis. Target enrollment is 300 patients with primary analysis at 210 events to detect potential superiority of each investigational treatment over pooled control. Secondary endpoints are overall survival, objective response, disease control rate, safety, pharmacokinetics, immunogenicity (ramucirumab), and patient reported outcomes. An exploratory endpoint is to correlate biomarkers with safety and clinical outcome; blood, plasma, serum, and tumor tissue collection is mandatory. The study began in May 2016. Clinical trial information: NCT02711553.
Utilizing total neoadjuvant therapy (TNT) in rectal cancer: NRG-GI002, a phase II clinical trial platform.
Authors: George Thomas J. , Yothers Greg , Hong Theodore S. , Russell Marcia McGory , You Y. Nancy , Parker William , Jacobs Samuel A. , Pogue-Geile Katherine L. , Wu Christina Sing-Ying , Wolmark Norman
Published: March 2017

TPS814

Background: Improvements in outcomes for locally advanced rectal cancer (LARC) have plateaued due to an inability to consistently deliver adjuvant therapy and thus far ineffective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers are needed to advance treatment outcomes. This randomized phase II modular clinical trial platform utilizes Total Neoadjuvant Therapy (TNT) with parallel experimental arms in LARC. The experimental arms are not intended for direct comparison, but to test a variety of sensitizers or hypotheses in a consistent and relatively homogenous high-risk patient (pt) population with correlative biomarkers. Success of any given experimental arm will be determined by achievement of pathologic endpoints compared to a control arm. Methods: This NCTN multi-arm randomized phase II trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC as defined by any ONE of the following criteria: distal location (cT3-4 ≤5cm from the anal verge, any N); bulky (any cT4 or tumor within 3mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, all pts receive neoadjuvant FOLFOX x 4mo → chemoRT (capecitabine with 50.4Gy) → surgical resection 8-12 wks later. Based on promising phase I results, the first experimental arm will assess the activity of veliparib added to standard chemoRT (capecitabine + RT). Primary endpoint is to demonstrate an improvement in Neoadjuvant Rectal Cancer (NAR) score for the experimental arm vs control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including quality of life, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts per arm with additional arms added through rolling protocol amendments. Support: U10 CA-180868, -180822, UG-189867; AbbVie. Clinical trial information: NCT02921256.
KEYNOTE-177: Randomized phase III study of pembrolizumab versus investigator-choice chemotherapy for mismatch repair-deficient or microsatellite instability-high metastatic colorectal carcinoma.
Authors: Diaz Luis A. , Le Dung T. , Yoshino Takayuki , Andre Thierry , Bendell Johanna C. , Koshiji Minori , Zhang Yinghua , Kang S. Peter , Lam Baohoang , Jäger Dirk
Published: March 2017

TPS815

Background: A subset of colorectal carcinomas (CRCs) are characterized by mismatch repair (MMR) deficiency resulting in microsatellite instability (MSI). MSI-high tumors contain high levels of lymphocyte infiltrates and express the PD-1 immune checkpoint receptor and its ligand, PD-L1. In the phase 2 KEYNOTE-016 study, the anti–PD-1 antibody pembrolizumab demonstrated antitumor activity against MMR-deficient tumors in patients with treatment-refractory metastatic CRC. KEYNOTE-177 (ClinicalTrials.gov, NCT02563002) is an international, randomized, open-label, phase 3 study of pembrolizumab versus standard-of-care (SOC) chemotherapy in first-line MMR-deficient or MSI-high metastatic CRC. Methods: Key eligibility criteria include age ≥18 years, confirmed MSI-high or MMR-deficient metastatic CRC, ECOG PS 0-1, no active autoimmune disease or brain metastases, and no prior therapy for metastatic disease. ~270 patients will be randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 weeks or investigator's choice of SOC chemotherapy (mFOLFOX6 or FOLFIRI alone or in combination with bevacizumab or cetuximab, chosen before randomization). Treatment is to continue until progressive disease (PD), unacceptable toxicity, patient/investigator decision, or completion of 35 cycles (pembrolizumab only). Response is to be assessed every 9 weeks per RECIST v1.1 by central imaging vendor review and per RECIST adapted for immunotherapy response patterns. Eligible patients may continue pembrolizumab beyond initial RECIST-defined progression. Patients in the SOC arm who have PD and meet crossover criteria may be eligible to receive pembrolizumab for up to 17 treatment cycles. AEs are to be assessed throughout treatment and for 30 days thereafter (90 days for serious AEs) and graded per NCI CTCAE v4.0. Patients are to be followed up for survival every 9 weeks. The primary end point is PFS per RECIST v1.1; key secondary end points include OS and ORR. Enrollment in KEYNOTE-177 is ongoing. Clinical trial information: NCT02563002.
Cancer survivorship care in rural community: Patient perspective.
Authors: Noyes Katia , Holub David , Rizvi Irfan , Swanger Alex , Reisdorf Coty , Tomaszewski Kenneth , Constine Louis S.
Published: March 2017

25

Background: Advances in oncologic sciences have resulted in successful treatments for many cancers with improved event-free and overall survival for millions of patients. Efficient delivery of state of the art cancer care requires well-orchestrated performances of multiple oncology, primary care and social services providers. However, many rural oncology providers do not offer such multidisciplinary cancer services and rely on patients to coordinate their own care. This study assessed perspectives of rural cancer patients and caregivers on their confidence to make decisions and address their care needs. Methods: We conducted focus groups with the attendees of 3 rural Congregate Meals. The county-sponsored programs bring together seniors for nutritional meals, social connectedness and educational programs. We also developed and piloted a 5-question survey, asking respondents to rate their confidence in interacting with their clinicians about care needs, care coordination and barriers to care. Results: Overall, 85 individuals participated in the focus groups and 76 persons returned the survey (90% response rate). The vast majority of the participants were cancer survivors or caregivers to patients with cancer. Transportation to and from oncology appointments presents a major concern for the rural communities, as most patients had to travel long distance to see a doctor. Patients also reported having difficulty making decisions regarding their care due to a lack of knowledge about specific cancer services and limited availability of providers. Cancer support groups, behavioral health providers, exercise and nutrition therapies were reported to be particularly scarce in rural areas. We found that patients who had trusted relationships with their physicians tended to be more confident in their ability to obtain necessary help from their providers compared to patients who reported poor communication and lack of trust. Conclusions: There are numerous reasons that may lead to rural-urban disparities in cancer survivorship outcomes including limited availability of supportive services, limited patient resources, burden of patient decision making and care coordination, and lack of adequate patient-provider communication.
The evolving role of the primary care provider in the comprehensive cancer care paradigm: Knowledge, attitudes, beliefs, and practices of primary care clinicians.
Authors: Van Londen G J. , Brufsky Jill Weiskopf , Parker Ira Russell
Published: March 2017

28

Background: Due to increasing numbers of individuals diagnosed with cancer, a burgeoning cohort of cancer survivors with significant medical co-morbidities, and oncology workforce challenges, the optimal integration of Primary Care Providers (PCPs) into the comprehensive cancer care paradigm is of timely importance. The goal of this investigation is to determine the knowledge, attitudes, beliefs, and practices of primary care clinicians -- pertaining to their existing and potential roles in cancer care. Methods: 1,069 clinical affiliates of the University of Pittsburgh Medical Center, who provide primary care services (e.g. Cardiology, Family Medicine, Geriatric Medicine, Gynecology, and Internal Medicine), were invited to participate in a 77-question, IRB-approved, online survey questionnaire [Qualtrics (Provo, Utah)]. Three “reminder emails” were generated. Results: Note: These results reflect the analysis of an initial, preliminary subset of survey responders (N=90). The full data set will be utilized for the final poster presentation. Eighty percent of the responders are physicians. Seventy-one percent reported that 50%+ of their time is spent providing primary care services and 66% have been in-practice for 15+ years. 73%, 63% and 59% respectively have participated in “cancer surveillance”, “cancer treatment/disease-related adverse event (AE) monitoring”, and “AE management” activities. Cardiotoxicity (42%), lymphedema (61%), and vasomotor flushing (63%) represented those AEs that the responders felt least comfortable monitoring independently. Twelve percent were aware of the PCP-targeted December/2015 “ACS-ASCO Breast Cancer Guideline” and 24% of the term “Survivorship Care Plan”. Twenty-two percent were “very confident” with regard to conducting a “low dose CT” lung cancer screening decision-making patient conversation. Twenty-one percent felt that their formal training did not adequately prepare them and that their present educational opportunities are inadequate pertaining to PCP-Cancer Survivorship issues. “Communication between the Oncology Team and PCP” was noted as the most stated “major issue”. Conclusions: To fully optimize the interface between Oncologists and PCPs with regard to best practices cancer care, strategies targeting competency training, enhanced information/guideline dissemination, and the development of collaborative-based delivery models will likely be necessary.
Methylprednisolone Therapy in Acute Traumatic Spinal Cord Injury: Analysis of a Regional Spinal Cord Model Systems Database
Authors: Sunshine Jacob E. , Dagal Armagan , Burns Stephen P. , Bransford Richard J. , Zhang Fangyi , Newman Shu-Fang , Nair Bala G. , Sharar Sam R.
Published: March 2017

BACKGROUND:

The objective of this study was to assess the relationship between exposure to methylprednisolone (MP) and improvements in motor function among patients with acute traumatic spinal cord injury (TSCI). MP therapy for patients with TSCI is controversial because of the current conflicting evidence documenting its benefits and risks.

METHODS:

We conducted a retrospective cohort study from September 2007 to November 2014 of 311 patients with acute TSCI who were enrolled into a model systems database of a regional, level I trauma center. We linked outcomes and covariate data from the model systems database with MP exposure data from the electronic medical record. The primary outcomes were rehabilitation discharge in American Spinal Injury Association (ASIA) motor scores (sum of 10 key muscles bilaterally as per International Standards for Neurological Classification of Spinal Cord Injury, range, 0–100) and Functional Independence Measure (FIM) motor scores (range, 13–91). Secondary outcomes measured infection risk and gastrointestinal (GI) complications among MP recipients. For the primary outcomes, multivariable linear regression was used.

RESULTS:

There were 160 MP recipients and 151 nonrecipients. Adjusting for age, sex, weight, race, respective baseline motor score, surgical intervention, injury level, ASIA Impairment Scale (AIS) grade, education, and insurance status, there was no association with improvement in discharge ASIA motor function or FIM motor score among MP recipients: −0.34 (95% CI, −2.8, 2.1) and 0.75 (95% CI, −2.8, 4.3), respectively. Adjusting for age, sex, race, weight, injury level, and receipt of surgery, no association with increased risk of infection or GI complications was observed.

CONCLUSIONS:

This retrospective cohort study involving patients with acute TSCI observed no short-term improvements in motor function among MP recipients compared with nonrecipients. Our findings support current recommendations that MP use in this population should be limited.
Refilins are short-lived Actin-bundling proteins that regulate lamellipodium protrusion dynamics
Authors: Gay Olivia , Gilquin Benoît , Assard Nicole , Stuelsatz Pascal , Delphin Christian , Lachuer Joël , Gidrol Xavier , Baudier Jacques
Published: March 2017

Refilins (RefilinA and RefilinB) are members of a novel family of Filamin binding proteins that function as molecular switches to conformationally alter the Actin filament network into bundles. We show here that Refilins are extremely labile proteins. An N-terminal PEST/DSG(X)2-4S motif mediates ubiquitin-independent rapid degradation. A second degradation signal is localized within the C-terminus. Only RefilinB is protected from rapid degradation by an auto-inhibitory domain that masks the PEST/DSG(X)2-4S motif. Dual regulation of RefilinA and RefilinB stability was confirmed in rat brain NG2 precursor cells (polydendrocyte). Using loss- and gain-of-function approaches we show that in these cells, and in U373MG cells, Refilins contribute to the dynamics of lamellipodium protrusion by catalysing Actin bundle formation within the lamella Actin network. These studies extend the Actin bundling function of the Refilin-Filamin complex to dynamic regulation of cell membrane remodelling.
‘Smart asthma’: What connected devices can mean for care
Authors: McMurray Ann
Published: March 2017

Asthma UK has recently published a report on the use of connected asthma devices in the delivery of care, looking at the benefits and potential problems. Ann McMurray discusses the findings.
Unprotected education finances: What this can mean for children
Authors: Feuchtwang Anna
Published: March 2017

You can ‘protect’ the education budget, but in this climate you can't protect schools' costs, argues Anna Feuchtwang
Relationships and sex education: Has the battle been won?
Authors: Henshaw Pete
Published: March 2017

There has been widespread relief and support at the government's intention to make PSHE and relationships and sex education compulsory. Attention now turns to the proposed new curriculum and what it should contain. Pete Henshaw reports
Family break-up: Supporting children and young people
Authors: Thornton Stephanie
Published: March 2017

Family break-up can have damaging effects on children and young people's mental and physical health and wellbeing. Stephanie Thornton looks at ways to support them through this difficult process and help reduce negative outcomes.
An introduction to mindfulness in irritable bowel syndrome
Authors: Smith Graeme D
Published: March 2017

Irritable bowel syndrome (IBS) is a functional bowel disorder, which globally accounts for up to half of all referrals to gastroenterologists. It is a particularly complex condition, which can have a detrimental effect on the patient's health-related quality of life and psychosocial wellbeing. In recent years, there has been an increasing trend in the use of non-pharmacological interventions in the management of IBS, including mindfulness-based treatments (MBT). In this clinical skills article, Graeme D Smith examines the role of mindfulness in the management of IBS from a gastrointestinal nursing perspective.
Evaluation of an on-site stay and play project for Gypsy and Traveller preschool children and families
Authors: Thrift Miranda
Published: March 2017

Gypsy and Traveller babies and preschool children appear to have minimal opportunities to enhance their developmental skills and socialisation through play. They are often delayed in areas such as fine motor skills, and speech and language, due to lack of play opportunities. The aim of this project was to provide fortnightly stay and play sessions on site, in partnership with children's centre engagement workers to maximise play opportunities and deliver health messages to families through encouragement, praise and positive role-modelling. During the 3-month trial period, attendance at the sessions varied from two to five mothers with three to seven children, and included transient children and their families visiting relatives on site. Evaluation methods used included a reflective observation after each session, client feedback and a register of attendees. The client feedback was positive and provided sufficient evidence to continue the sessions after the trial period had ended. It is hoped that this role-modelling of play and interaction will cascade through the generations, improve long-term health outcomes and reduce health inequalities in Gypsy and Traveller communities.
What will genomics mean for you?
Authors: Oldman Crystal
Published: March 2017

In the next few years, probably sooner rather than later, there is going to be a major change in the conversations we have with the families with whom we work. The reason for this is the rapid developments in genomics research, says Crystal Oldman.
Driving progress in MFL
Authors: Pethybridge Anna
Published: March 2017

Lead practitioner Anna Pethybridge discusses her school's work to drive up progress in MFL, including a focus on teaching and learning and effective staff deployment
Um olhar sob a perspectiva do Projeto Pedagógico de Curso (PPC) do curso de Bacharelado em Administração: um estudo de caso na Universidade Federal de São Carlos - UFSCar
Authors: Oliveira Edenis Cesar de
Published: March 2017

O presente estudo teve como objetivo investigar a percepção crítica sobre o PPC do Curso de Administração da UFSCar – campus Lagoa do Sino, sob a perspectiva dos atores mais diretamente envolvidos com esse instrumento. Assentado sobre os pressupostos do paradigma interpretativo, utilizou-se um modelo qualitativo de pesquisa, de caráter exploratório. Como instrumento de coleta de dados, serviu-se da análise documental, questionário e observação participante. Os principais resultados apontam que, de um modo geral, o Projeto Pedagógico de Curso (PPC) traduz-se numa ferramenta de importância na gestão do curso. Contudo evidenciou-se necessidade de maior ênfase na divulgação desse instrumento no âmbito da comunidade acadêmica. Não obstante a isso, a funcionalidade e consolidação da metodologia proposta pelo PPC exigem de todos os atores envolvidos um esforço de gestão acadêmica com objetivos claros, pautados numa agenda funcional, construída e praticada a várias mãos. Em suma, a gestão acadêmica, vista sob essa ótica, carece de uma reformulação nos seus processos de execução, sobretudo no que diz respeito ao controle, no sentido de construir canais formais de aferição dos resultados do modelo implementado, consequentemente, gerando condições de retroalimentar o sistema e aprimorá-lo constantemente.
Script as a hypothesis: Scriptwriting for documentary film
Authors: Aaltonen Jouko
Published: March 2017

Writing the script for a documentary film can be problematic. According to some documentary filmmakers, it is not possible at all, because one cannot know beforehand what is going to happen. Nonetheless, a written script is often required to obtain financing for a documentary project. This article deals with different work practices and forms of documentary script. It analyses two case studies: the writer’s own films A Man from the Congo River (2010) and Kusum (2000). The first is the story of an engineer who worked in colonial Congo at the beginning of the twentieth century. It is based on diaries and other historical material, and therefore it was possible to construct a very precise script for the film. Kusum is an observational documentary film following the healing of a young Indian girl. The script was produced prior to production, but during the shooting process many core elements changed, including the main character and storyline. The form and dramaturgy of documentary films are created in the filmmaking process and in dialogue between the filmmaker and real people. A documentary script can be considered a hypothesis about the reality that the filmmaker will encounter via the process of filmmaking. Instead of ‘a screen idea’ we could speak about ‘a documentary idea’.
Differences in the stratum corneum of Indonesian infants and adults
Authors: Fujimura Tsutomu , Shima Kyoko , Miyauchi Yuki , Hotta Mitsuyuki , Hashimoto Hiroshi , Yunaidi Danang Agung , Putri Ratih Sofia Ika , Ningrum Puspita , Takema Yoshinori
Published: March 2017

Background Although understanding the stratum corneum (SC) of infant skin is important to avoid skin diseases such as atopic dermatitis, there has been no such investigation in Indonesian infants to date.Objective  To obtain a basic knowledge of SC characteristics in Indonesian infants in order to develop methods for infant-specific skin care and to prevent dermatitis and infection.Methods Seventy-two healthy, full term infants aged 1 to 24 months who were native Indonesians residing in Jakarta were enrolled in this study. Some of the mothers were also enrolled in the study as adults (n=30). Transepidermal water loss (TEWL) and hydration of the SC (capacitance) on the thigh, buttock, and upper arm were measured after sufficient acclimation in an air-conditioned room, in both infants and mothers. Results The SC hydration was significantly higher in infants than adults at all sites measured, including the buttocks, which is a diaper area. Infant TEWL values were also significantly higher than in adults at all sites. Hydration of the SC and TEWL values showed no significant correlation with age of infant for any site. The SC hydration and TEWL values of Indonesian infants did not decrease to adult values within 24 months, which indicates that the SC characteristics in infants continue to develop after 24 months of age.Conclusion  Indonesian infants aged 0-24 months have significantly higher SC hydration and TEWL values than Indonesian mothers. However, infant age has no correlation to SC hydration or to TEWL values.
A retomada da vibrante em coda final em ambientes on-line e off-line: a internet influenciou a escrita dos alunos
Authors: Damulakis Gean Nunes , Queiroz Verônica Tozzo
Published: March 2017

Este estudo tem foco no cancelamento da vibrante em coda final de palavra na escrita de escolares e investiga a possibilidade de espelhamento da fala. Trata-se aqui da consciência da díade fala e escrita que os noviços em processo de letramento devem apresentar, tanto mais rápido melhor, de modo a evitar erros ortográficos provenientes de fenômenos variáveis na fala, ainda que sejam comuns e não estejam, muitas vezes, sujeitos a estigmas. Partindo dos resultados de Queiroz (2016), debruça-se aqui sobre interações entre os alunos por meio digital – mais precisamente através do aplicativo WhatsApp em um comparativo com a escrita em suporte tradicional. O intuito é confrontar dois ambientes nos quais a escrita dos alunos se concretiza, o ambiente on-line e o off-line, para responder à pergunta de pesquisa.
A produção de textos no Ensino Fundamental: desenvolvendo a competência escrita por meio de sequência didática
Authors: Paiva Hermínia Maria Florêncio , Zavam Aurea Suely
Published: March 2017

Este trabalho é fruto de um projeto de pesquisa que tem como objetivo principal a aplicação de uma sequência didática para trabalhar com um gênero da ordem do argumentar: a carta de reclamação, com alunos do 9º ano do Ensino Fundamental. O propósito maior é desenvolver nos alunos habilidades de leitura e escrita como práticas sociais imprescindíveis em nossa sociedade letrada. A proposta parte da concepção de escrita como processo (VIEIRA, 2005) e fundamenta-se no modelo de sequência didática (SD) de Dolz, Noverraz e Schneuwly (2004). Com os resultados alcançados, constata-se que o trabalho com a sequência didática, além de melhorar o desempenho na produção de textos escritos, proporciona o (re)conhecimento do gênero, conforme defendem os autores do modelo de SD. A experiência possibilita verificar avanços nas produções dos alunos tanto em relação à apropriação dos elementos prototípicos da carta de reclamação quanto à habilidade do processo de escrita, além de favorecer a percepção de um maior estímulo dos estudantes com o desenvolvimento de um projeto próprio para a produção de textos. Nesse sentido, espera-se contribuir com professores de Língua Portuguesa, tanto no que se refere ao ensino da produção de textos quanto no que toca à busca de novas alternativas para potencializar habilidades nos estudantes e aumentar a motivação para que escrevam com mais propriedade e com mais frequência.
Estrogen maintains mitochondrial content and function in the right ventricle of rats with pulmonary hypertension
Authors: Liu Aiping , Philip Jennifer , Vinnakota Kalyan C. , Van den Bergh Francoise , Tabima Diana M. , Hacker Timothy , Beard Daniel A. , Chesler Naomi C.
Published: March 2017

The typical cause of death in pulmonary hypertension (PH) is right ventricular (RV) failure, with females showing better survival rates than males. Recently, metabolic shift and mitochondrial dysfunction have been demonstrated in RV failure secondary to PH. In light of evidence showing that estrogen protects mitochondrial function and biogenesis in noncardiovascular systems, we hypothesized that the mechanism by which estrogen preserves RV function is via protection of mitochondrial content and oxidative capacity in PH. We used a well‐established model of PH (Sugen+Hypoxia) in ovariectomized female rats with/without estrogen treatment. RV functional measures were derived from pressure–volume relationships measured via RV catheterization in live rats. Citrate synthase activity, a marker of mitochondrial density, was measured in both RV and LV tissues. Respiratory capacity of mitochondria isolated from RV was measured using oxygraphy. We found that RV ventricular‐vascular coupling efficiency decreased in the placebo‐treated SuHx rats (0.78 ± 0.10 vs. 1.50 ± 0.13 in control, P < 0.05), whereas estrogen restored it. Mitochondrial density decreased in placebo‐treated SuHx rats (0.12 ± 0.01 vs. 0.15 ± 0.01 U citrate synthase/mg in control, P < 0.05), and estrogen attenuated the decrease. Mitochondrial quality and oxidative capacity tended to be lower in placebo‐treated SuHx rats only. The changes in mitochondrial biogenesis and function paralleled the expression levels of PGC‐1α in RV. Our results suggest that estrogen protects RV function by preserving mitochondrial content and oxidative capacity. This provides a mechanism by which estrogen provides protection in female PH patients and paves the way to develop estrogen and its targets as a novel RV‐specific therapy for PH.
Trunk muscle activation during movement with a new exercise device for lumbo‐pelvic reconditioning
Authors: Weber Tobias , Debuse Dorothée , Salomoni Sauro E. , Elgueta Cancino Edith L. , De Martino Enrico , Caplan Nick , Damann Volker , Scott Jonathan , Hodges Paul W
Published: March 2017

Gravitational unloading leads to adaptations of the human body, including the spine and its adjacent structures, making it more vulnerable to injury and pain. The Functional Re‐adaptive Exercise Device (FRED) has been developed to activate the deep spinal muscles, lumbar multifidus (LM) and transversus abdominis (TrA), that provide inter‐segmental control and spinal protection. The FRED provides an unstable base of support and combines weight bearing in up‐right posture with side alternating, elliptical leg movements, without any resistance to movement. The present study investigated the activation of LM, TrA, obliquus externus (OE), obliquus internus (OI), abdominis, and erector spinae (ES) during FRED exercise using intramuscular fine‐wire and surface EMG. Nine healthy male volunteers (27 ± 5 years) have been recruited for the study. FRED exercise was compared with treadmill walking. It was confirmed that LM and TrA were continually active during FRED exercise. Compared with walking, FRED exercise resulted in similar mean activation of LM and TrA, less activation of OE, OI, ES, and greater variability of lumbo‐pelvic muscle activation patterns between individual FRED/gait cycles. These data suggest that FRED continuously engages LM and TrA, and therefore, has the potential as a stationary exercise device to train these muscles.
Wintering sites of Wallcreeper Tichodroma muraria on the east Adriatic coast
Authors: Lukač Gordan , Vujčić-Karlo Snježana , Ružanović Zlatko , Adžić Ivana , Milovac Marijan , Stelko Roberto
Published: March 2017

Wallcreeper Tichodroma muraria was observed during cold winters in different parts of Croatia, along the Adriatic coast, on islands as well as inland. Their origin remains unknown, but they may belong to the population nesting in the Alps or in Dinaric parts of Bosnia and Herzegovina and Montenegro. The overwintering along the Adriatic coast was explored during field observations, but also from the literature and museum data. The field investigations were carried out in Istria, North Dalmatia, Paklenica NP, Kornati NP and central Dalmatia, Krka NP. In total, 96 observations were made: 35 specimens from museum collections and literature and 61 during field research. The Wallcreeper was observed in Velika and Mala Paklenica canyons in Paklenica NP during cold winters, but not during milder winters. In the Paklenica NP, the earliest individuals were observed on 10 Oct and the latest on 28 Apr. On the complete east Adriatic coast and in Croatian inland, the earliest record was made on 6 Sep and the latest on 2 May. There are 5-10 individuals overwintering in Paklenica National Park.
Application of Interval Arithmetic to Production Planning in a Foundry
Authors: Duda J. , Stawowy A.
Published: March 2017

A novel approach for treating the uncertainty about the real levels of finished products during production planning and scheduling process is presented in the paper. Interval arithmetic is used to describe uncertainty concerning the production that was planned to cover potential defective products, but meets customer’s quality requirement and can be delivered as fully valuable products. Interval lot sizing and scheduling model to solve this problem is proposed, then a dedicated version of genetic algorithm that is able to deal with interval arithmetic is used to solve the test problems taken from a real-world example described in the literature. The achieved results are compared with a standard approach in which no uncertainty about real production of valuable castings is considered. It has been shown that interval arithmetic can be a valuable method for modeling uncertainty, and proposed approach can provide more accurate information to the planners allowing them to take more tailored decisions.
Preliminary Tests of Cellular SiC/Iron Alloy Composite Produced by a Pressureless Infiltration Technique
Authors: Lipowska B. , Psiuk B. , Cholewa M. , Kozakiewicz Ł.
Published: March 2017

Preliminary tests aimed at obtaining a cellular SiC/iron alloy composite with a spatial structure of mutually intersecting skeletons, using a porous ceramic preform have been conducted. The possibility of obtaining such a composite joint using a SiC material with an oxynitride bonding and grey cast iron with flake graphite has been confirmed. Porous ceramic preforms were made by pouring the gelling ceramic suspension over a foamed polymer base which was next fired. The obtained samples of materials were subjected to macroscopic and microscopic observations as well as investigations into the chemical composition in microareas. It was found that the minimum width of a channel in the preform, which in the case of pressureless infiltration enables molten cast iron penetration, ranges from 0.10 to 0.17 mm. It was also found that the ceramic material applied was characterized by good metal wettability. The ceramics/metal contact area always has a transition zone (when the channel width is big enough), where mixing of the components of both composite elements takes place.
The Evaluation of Mechanical Properties of High-tin Bronzes
Authors: Nadolski M.
Published: March 2017

High-tin bronzes are used for church bells and concert bells (carillons). Therefore, beside their decorative value, they should also offer other functional properties, including their permanence and good quality of sound. The latter is highly influenced by the structure of bell material, i.e. mostly by the presence of internal porosity which interferes with vibration of the bell waist and rim, and therefore should be eliminated. The presented investigations concerning the influence of tin content ranging from 20 to 24 wt% on mechanical properties of high-tin bronzes allowed to prove the increase in hardness of these alloys with simultaneous decrease in the tensile and the impact strengths (Rm and KV, respectively) for the increased tin content. Fractures of examined specimens, their porosity and microstructures were also assessed to explain the observed regularities. A reason of the change in the values of mechanical properties was revealed to be the change in the shape of α-phase crystals from dendritic to acicular one, and generation of grain structure related to the increased Sn content in the alloy.