bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative radiotherapy for high-risk prostate cancer (PORT-PC) trial.
Authors: Nagar Himanshu , Formenti Silvia , Scherr Douglas , Hu Jim C. , Schlegel Peter , Kang Josephine , Robinson Brian D. , Khani Francesca , Nanus David M. , Tagawa Scott T. , Molina Ana M. , Faltas Bishoy Morris , Margolis Daniel , Barbieri Christopher
Published: March 2019

TPS137

Background: Prostatectomy has become the most common treatment for high-risk prostate cancer. After prostatectomy, risk features for local recurrence include extra-capsular extension and/or seminal vesicle invasion (pT3 disease) and positive surgical margins. Post-operative radiotherapy is recommended for patients with pT3 disease, positive margins and/or Group Grade 4-5 and has been shown to reduce the risk of recurrence. In planning adjuvant radiotherapy, the clinical target volume is the prostate bed which is difficult to delineate once the prostate has been surgically removed and can be overestimated by following the location of surgical clips. As such, controversy exists as to the optimal target volume. Guidelines suggest including a significant portion of the posterior and inferior aspects of the bladder, and anterior aspect of the rectum exposing a significant amount of normal tissue to high dose radiation. Pre-operative radiotherapy potentially offers the following advantages: 1) reduced radiation dose to normal tissues; 2) ability to utilize stereotactic body radiotherapy (SBRT) with real-time MRI guidance 3) patient convenience with less fractions and 4) radiobiologic advantage of high dose per fraction treatment delivery. Methods: This is a modified dose escalation trial for patients with high-risk prostate cancer defined as cT3 on MRI or Group Grade 4-5 disease. Patients will sequentially undergo 1) placement of a rectal SpaceOAR, 2) SBRT on the ViewRay MRIdian linear accelerator and 3) prostatectomy. As a modified dose escalation study, patients will be accrued starting at 5 Gy x 5 (up to 8 Gy x 5) with 3 patients per cohort with Grade 4 or 5 gastrointestinal (GI) and/or genitourinary (GU) adverse event related to preoperative radiotherapy as an unacceptable dose limiting toxicity.The primary endpoint is that a patient can undergo a radical prostatectomy after SBRT without a post-operative GI or GU grade 4 or 5 toxicity within 30 days related to preoperative radiotherapy. Secondary objectives include assessment of acute toxicity and quality of life scores. Exploratory analyses include analysis of tumor and normal biopsied and resected tissue and serum markers and interpretation of pre- and post-SBRT MRIs. Clinical trial information: NCT03663218.
A phase II trial in progress: Pamiparib, an investigational PARP inhibitor, in patients with metastatic castration-resistant prostate cancer and a circulating tumor cell homologous recombination deficiency (HRD) phenotype or BRCA defects.
Authors: Chowdhury Simon , Mateo Joaquin , Gross Mitchell , Armstrong Andrew J. , Cruz-Correa Marcia , Piulats Josep M. , Blay Jean-Yves , Rivas Delcia , Quintero Luis , Castro Henry , Nkobena Andong , Raponi Mitch , Pelham Robert , Landers Mark Andrew , Montgomery Robert B.
Published: March 2019

TPS328

Background: Men with metastatic castration-resistant prostate cancer (mCRPC) who have a BRCA1/2 mutation ( BRCA1/2mut) or mutations in other HRD genes have a poor prognosis. The EPIC liquid biopsy test is a novel assay that can identify circulating tumor cells (CTC) with HRD associated phenotypes. Preliminary studies have shown that these men may respond to treatment with a PARP inhibitor. Pamiparib is an investigational PARP1/2 inhibitor that has shown brain penetration and potent PARP–DNA complex trapping in nonclinical studies. In early phase clinical studies (NCT02361723; NCT03333915), pamiparib was generally well tolerated and showed preliminary antitumor activity; 60 mg orally twice daily (BID) was established as the recommended investigational dose. Methods: This open-label, global, phase 2 study (NCT03712930) will evaluate antitumor activity and safety of pamiparib in mCRPC pts with CTC-HRD, assessed by the EPIC CTC-HRD assay, or deleterious germline/somatic BRCA1/2mut status. Patients must have progressed on/after ≥1 androgen receptor-targeted therapy, have received ≥1 taxane-based therapy, and have prostate-specific antigen (PSA) progression per PCWG3 criteria. Four cohorts of patients will receive pamiparib 60 mg BID in 28-day cycles. Cohort 1 will include ~50 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with measurable metastatic disease; Cohort 2 will include ~30 pts with CTC-HRD+ +/- BRCA1/2mut mCRPC with bone-only disease; Cohorts 3 & 4 will include ~20 pts with CTC-HRD-/unknown + BRCA1/2mut mCRPC with measurable metastatic disease (Cohort 3), or bone-only disease (Cohort 4). Disease status will be assessed every 8 wks for 24 wks, then every 12 wks; PSA levels will be tested every 4 wks. Co-primary endpoints are radiographic ORR assessed by IRC (pts with measurable disease) and confirmed PSA response rate per PCWG3 criteria (pts +/- measurable disease). Secondary endpoints include ORR, time to PSA response/progression, duration of PSA response, time to symptomatic skeletal event, radiographic progression-free survival, overall survival, and safety. Clinical trial information: NCT03712930.
A phase II study of onvansertib (PCM-075) in combination with abiraterone and prednisone in patients with metastatic castration-resistant prostate cancer.
Authors: Einstein David Johnson , Choudhury Atish Dipankar , Saylor Philip James , Werner Lillian , Erlander Mark G. , Ridinger Maya , Bubley Glenn
Published: March 2019

TPS336

Background: Metastatic castration-resistant prostate cancer (mCRPC) remains a leading cause of cancer-related deaths worldwide. Although abiraterone (abi) in either the castration-sensitive or castration-resistant setting increases survival, resistance is universal and limits the efficacy of subsequent hormonal therapies. Polo-like kinase 1 (PLK1) is a serine/threonine protein kinase that regulates mitotic functions and promotes the progression of cells through mitosis, and it is highly upregulated in prostate cancer following castration. PLK1 inhibition enhances the efficacy of abi in cell line models as well as patient-derived tumor xenografts via several mechanisms. Onvansertib (PCM-075; Trovagene, Inc.) is the first orally available PLK1-specific inhibitor. In phase 1 testing, onvansertib demonstrated a manageable safety profile, with transient hematologic effects as its most prominent, yet reversible, toxicity. Methods: The goal of this phase 2 study (NCT03414034) is to observe the effects of onvansertib in combination with abi + prednisone on disease control, as assessed by prostate-specific antigen (PSA) decline or stabilization after 12 weeks of study treatment, in subjects with mCRPC and early resistance to abi. Patients will be enrolled at time of PSA progression while on standard abi. A completed 3-patient safety lead-in phase tested the safety of the combination of onvansertib with abi, and the accruing expansion phase will treat 29 more patients with onvansertib (24 mg/m2 orally on days 1-5 of a 21-day cycle) plus abi (administered orally and continuously once daily with prednisone) until time of radiographic or symptomatic progression. With 32 patients, there will be 90% power to detect a change in disease-control rate from 10% (null) to 30% (alternative). Based on a Simon’s two-stage optimal design, the study will terminate early if < 2 of the first 13 patients achieve disease control. Exploratory analyses include evaluations of predictive genomic biomarkers in circulating tumor cells and circulating tumor DNA, including alterations of oncogenes and tumor suppressors implicated in PLK1 sensitivity within preclinical models. Clinical trial information: NCT03414034.
A randomized phase II study comparing cabazitaxel/prednisone to cabazitaxel alone in docetaxel-pretreated men with metastatic castration resistant prostate cancer (mCRPC): The CABACARE trial.
Authors: Buonerba Carlo , Grillone Francesco , Rossetti Sabrina , Livi Lorenzo , Scartozzi Mario , Tagliaferri Pierosandro , Bruzzese Dario , Scafuri Luca , Riccio Vittorio , Costabile Ferdinando , Bosso Davide , Iaccarino Simona , Facchini Gaetano , Carrano Simone , Izzo Michela , Caraglia Michele , De Placido Sabino , di Lorenzo Giuseppe
Published: March 2019

TPS345

Background: In the TROPIC trial, cabazitaxel (CAB) plus daily prednisone (PDN) was associated with a significant advantage in OS and PFS in docetaxel (DOC)-pretreated patients (Pts). Whether daily PDN may significantly contribute to CAB efficacy or improve its safety profile is unknown. In the CHARTEED trial, DOC was administered without daily PDN with no concerns about the lack of efficacy or greater toxicity. Safety data about CAB without PDN are scarce. Corticosteroids present multiple biological effects, which may potentially be either positive, such as those mediated by adrenal androgen and cytokine suppression, or detrimental, such as those associated with the activation of the glucocorticoid receptor (GR) and of the androgen receptor (AR). Furthermore, PDN is a CYP3A4 inducer and can potentially negatively affect CAB clearance. Finally, AR-V7 positivity in circulating tumor cells and retinoblastoma (RB) loss/inactivation have been identified as potential mechanisms of resistance to hormonal and chemotherapy treatments in prostate cancer. For this reason, we also aim to evaluate if CAB activity is related to such biomarkers. Methods: CABACARE (EudraCT 2016-005251-25) is a randomized, phase II, open label, multi-center study comparing CAB at 25 mg/m2 q21 plus daily PDN (10 mg) vs CAB at 25 mg/m2 q21 alone in mCRPC pts progressed during or after DOC treatment. The study is designed to test non inferiority in terms of PFS, according PCWG-2, of CAB alone vs CAB plus PDN assuming that the two arms are equally effective (non-inferiority HR = 1.4). Main secondary objectives are: safety, QoL, pain assessment, overall response rate (ORR), PSA response, time to PSA progression, Time to radiological progression; OS; time to skeletal related events . The influence of AR-V7 and RB status measured in circulating epithelial cells at baseline on CAB activity will also be evaluated. A total of 35 Italian centers have started / will start recruiting pts in the CABACARE trial. Of the 220 pts required by the trial design, 43 pts have been enrolled since 30th Nov , 2017 until 2nd Oct, 2018 in 10 different Italian Institutions. Clinical trial information: 2016-005251-25.
Metacure: Multi-arm multimodality therapy for very high risk localized and low volume metastatic prostatic adenocarcinoma.
Authors: Teo Min Yuen , Taplin Mary-Ellen , Eastham James Andrew , Benoliel Hannah , Kibel Adam S. , McBride Sean Matthew , Nguyen Paul L. , Gopalan Anuradha , Lis Rosina , Scher Howard I.
Published: March 2019

TPS349

Background: Therapeutic advances in the management of metastatic castration-resistant prostate cancer (mCRPC) have not been matched in non-castrate states. A key obstacle is the traditional paradigm in which therapies with significant benefit in mCRPC are then studied in patients (pts) with localized, rising PSA or early metastatic disease using time-to-event (TTE) outcomes (e.g. biochemical recurrence, radiographic progression or death). These trials are costly, lengthy and often give inconclusive results that do not change practice nor provide a methodology to rank regimens based on efficacy. A new strategy is needed that gives a rapid efficacy readout and prioritizes approaches for large-scale testing. Methods: Metacure is a multi-arm, multi-stage randomized Phase 2 trial in which novel systemic therapies are studied in the context of a multimodality approach, which includes radical prostatectomy + pelvic and retroperitoneal lymph node dissection, if applicable, stereotactic radiotherapy (RT) to osseous metastases, and an option for adjuvant RT based on risk factors. The arms include combinations of ADT + apalutamide +/- abiraterone acetate and prednisone. Non-castrate prostate cancer pts with high probability of relapse or death from disease ranging from very high risk localized to low-volume metastatic disease are eligible. The primary endpoint is pathologic complete response and minimal residual disease. The secondary endpoint is undetectable PSA with non-castrate levels of testosterone. Both are binary endpoints that circumvent interpretations of the clinical relevance of TTE outcomes, providing a read-out of success or failure in a shorter time frame with fewer pts. The uniform entry criteria and continuous randomization enables ranking and prioritization of the strategies evaluated for further development in large-scale trials so that only the most effective ones move forward. This multicenter trial is managed by the Prostate Cancer Clinical Trials Consortium, funded by Janssen and is currently open and actively accruing. Future plans include opening a cohort of pts with aggressive non-castrate disease harboring DNA damage repair alterations. Clinical trial information: NCT03436654.
A phase I-II study to evaluate safety and efficacy of the combination of niraparib plus cabozantinib in patients with advanced kidney/urothelial carcinoma.
Authors: Font Pous Albert , Climent Duran Miguel Angel , Duran Ignacio , Mellado Begona , Paramio Jesus , Real Francisco X. , Ramirez Jose Luis , Sanz Juan Luis , Castellano Daniel E.
Published: March 2019

TPS501

Background: Niraparib (N) is an orally selective poly(ADP-ribose) polymerase (PARP)-1/-2 inhibitor approved for maintenance treatment of patients (pt) with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer after complete or partial response to platinum-based chemotherapy (CT). Cabozantinib (C) is a tyrosine kinase (TK) inhibitor with activity against TKs including VEGFR2, MET and AXL, approved on kidney cancer pt after TK failure, that has demonstrated clinical activity in heavily pretreated, advanced UC pt. c-Met receptor TK is activated in urothelial carcinoma (UC) cells. c-Met activity can decrease response to PARP inhibitors, whereas treatment with c-Met inhibitors renders cells more sensitive to PARP inhibition. UC pt with tumors overexpressing c-Met may benefit from the combination of c-Met and PARP inhibitors. This multicenter, open-label phase (ph) I-II study is to explore the maximum-tolerated dose (MTD) of N + C combination in pt with advanced genitourinary malignancies (UC and kidney cancer) follow by a preliminary efficacy of the combination in advanced UC. Methods: Eligible pt have confirmed histopathology of UC or clear cell renal cell carcinoma, advanced or metastatic disease, age ≥18 years, ECOG PS ≤1, progressive disease after platinum-based CT, measurable lesions, no prior therapy with PARP or c-Met inhibitors and adequate bone marrow, liver and renal functions. The ph I portion is enrolling ≈24 pt to identify the MTD proposed to use in a ph II (RP2D). Pt will receive N and C p.o. once daily in 28-day cycles: Dose level 1 (DL1) N/C 100/20 mg; DL2 200/20 mg; DL3 200/40 mg; DL4 200/60 mg. Pt will be accrued to each dose level in cohorts of 6 pt until the MTD is achieved (the highest dose at which ≤1 out of 6 pt experience a dose-limiting toxicity [DLT]). DLT will be evaluated during the first 2 cycles. The ph 2 portion will enroll 51 UC pt to receive the RP2D. Tumor response will be assessed per RECIST v1.1. Endpoints of the ph 2 are 6-month PFS (primary), overall response rate, disease control rate, duration of response, PFS and OS. Tissue and plasma sample will be collected for translational study. Clinical trial information: NCT03425201.
CANTATA: Randomized, international, double-blind study of CB-839 plus cabozantinib versus cabozantinib plus placebo in patients with metastatic renal cell carcinoma.
Authors: Tannir Nizar M. , Agarwal Neeraj , Dawson Nancy Ann , Motzer Robert J. , Jacobs Carmel Maree , Choueiri Toni K. , Hrom John Stewart , Geynisman Daniel M. , Davis Nancy B. , Figlin Robert A. , O'Keeffe Mary Kathleen , Parikh Jigarkumar R. , Vaena Daniel A. , Liu Ping-Yu , O'Keeffe Bridget , Tran Xuan , Escudier Bernard
Published: March 2019

TPS682

Background: Glutamine metabolism is upregulated in renal cell carcinoma (RCC) and important for RCC tumor cell proliferation and survival. CB-839 is a first-in-clinic, potent, oral inhibitor of the mitochondrial enzyme glutaminase (GLS), which controls a critical step in tumor cell metabolism of glutamine. CB-839 demonstrated synergistic anti-tumor activity when combined with cabozantinib, a VEGFR2/MET/AXL inhibitor, in preclinical RCC models. In a phase 1 study cohort, CB-839 plus cabozantinib as 2L+ therapy showed encouraging safety and efficacy results, with 50% overall response rate (ORR; RECIST v1.1) and 100% disease control rate in 10 patients with clear cell advanced/metastatic RCC (mRCC). A randomized, double-blind study comparing CB-839 plus cabozantinib vs. cabozantinib plus placebo has been initiated in patients with clear cell mRCC. Methods: In this ongoing international, randomized, double-blind, multi-center study, enrollment is planned for ~300 patients with clear cell mRCC. To be eligible, patients should have received 1-2 prior lines of systemic therapy for mRCC including ≥1 anti-angiogenic therapy or the combination of nivolumab + ipilimumab, have KPS ≥70%, measurable disease (RECIST v1.1), and no prior cabozantinib (or other MET inhibitor). Patients are randomized 1:1 to receive either CB-839 (800 mg twice daily per oral [PO] route) plus cabozantinib (60 mg daily PO) or cabozantinib plus placebo in 28-day cycles until disease progression or unacceptable toxicity. Patients are stratified by prior PD-1/PD-L1 inhibitor therapy and by IMDC prognostic risk group (favorable vs. intermediate vs. poor). The primary endpoint is progression-free survival (PFS) per RECIST v1.1, determined by blinded independent radiology review. Secondary endpoints are investigator-assessed PFS and overall survival. Safety, response per RECIST, and quality of life are also assessed. Findings of this randomized, international clinical trial will inform the efficacy and safety profile of CB-839, a first-in-clinic metabolic inhibitor, in combination with cabozantinib in patients with mRCC. Clinical trial information: NCT03428217.
An Integrative Review of the Barriers to Indigenous Peoples Participation in Biobanking and Genomic Research
Authors: Aramoana Jaclyn , Koea Jonathan ,   on behalf of the CommNETS Collaboration
Published: March 2019

PURPOSE

This investigation was undertaken to define the barriers to Indigenous peoples participating in biobanking and genomic research.

METHODS

A literature review was conducted to identify studies reporting on the experience of Indigenous peoples with biobanking, tissue banking, and genomic research. Studies pertaining to organ transplantation or blood donation for transfusion were excluded. The databases searched were MEDLINE, EMBASE, PubMed, Web of Science, and Google Scholar, with all literature available until the search date of June 1, 2018, included. The reference lists of all included papers, as well as related review articles, were manually searched to identify additional relevant studies. An inductive approach was used to identify common themes.

RESULTS

Seventeen publications discussed the experiences of New Zealand Māori (n = 2), Aboriginal and Torres Strait Islanders (n = 3), Native Hawaiian (n = 4), Native Alaskan (n = 2), American First Nation (n = 2), or multiple ethnicities (n = 4). Across all Indigenous peoples, four themes emerged: land, ancestors, culture, and bodily substances are powerfully interconnected and can act on each other; tissue and blood can provide important information (both Western and traditional) about a person; the ownership of specimens—custodians, trustees, or guardians; and the beneficence of the researchers and research team.

CONCLUSION

Indigenous communities, like Western populations, are concerned with issues pertaining to handling, treatment, and ownership of tissue as well as knowledge gained from specimen analysis. Unlike many Western populations, Indigenous communities have retained a strong sense of cultural connection to ancestors and traditional lands and view biologic specimens as inseparable from these things.
Two Incompletes
Authors: Schestag Thomas
Published: March 2019

This essay gathers two contributions to conferences or panels delivered in 2015 and 2016. The liminal figure relating both incompletes is the Sammler, as discussed in two texts by Walter Benjamin: “Eduard Fuchs, der Sammler und der Historiker” (“Eduard Fuchs: Collector and Historian”) and “Ich packe meine Bibliothek aus: Eine Rede über das Sammeln” (“Unpacking My Library: A Talk about Collecting”).
Between Friends
Authors: Ruffin Jessica , Stirner Simone
Published: March 2019

In this experimental essay authors and friends Jessica Ruffin and Simone Stirner explore the question of friendship through a dialogic exchange, engaging with friendship as a theoretical concept alongside their own personal histories and relationships. Emails exchanged beneath and between the dialogue lay bare the various registers of friendship and collaboration.
Spotlight on zebrafish: the next wave of translational research
Authors: Patton E. Elizabeth , Tobin David M.
Published: March 2019

Five years after the launch of the Disease Models & Mechanisms (DMM) Special Issue on zebrafish as a disease model, the field has progressed significantly. Zebrafish have been used to precisely model human genetic variants, to unpick the mechanisms of metabolic and other diseases, to study infection, inflammation and cancer, and to develop and test new therapeutic approaches. In this Editorial, we highlight recent research published in DMM that uses zebrafish to develop new experimental tools and to provide new insight into disease mechanism and therapy. The broad spectrum of subjects and approaches covered in these articles underscores the versatility of zebrafish in translational research. Further, it highlights the zebrafish community's ethos of creativity and collaboration in translating basic biological research into clinically relevant advances affecting how we understand and treat human disease.
Effects of Exercise on Stress-induced Attenuation of Vaccination Responses in Mice
Authors: SUN YI , PENCE BRANDT D. , WANG SELENA SHIYUE , WOODS JEFFREY A.
Published: March 2019

Studies suggest that exercise can improve vaccination responses in humans. Chronic stress can lead to immunosuppression, and there may be a role for exercise in augmenting immune responses.

Purpose

To investigate the effects of acute eccentric exercise (ECC) and voluntary wheel exercise training (VWR) on antibody and cell-mediated immune responses to vaccination in chronically stressed mice. We hypothesized that both ECC and VWR would attenuate chronic stress-induced reductions in vaccination responses.

Methods

Mice were randomized into four groups: control (CON), stress (S)-ECC, S-VWR, and S-sedentary (SED). Stressed groups received chronic restraint stress for 6 h·d−1, 5 d·wk−1 for 3 wk. After the first week of stress, S-ECC were exercised at 17 m·min−1 speed at −20% grade for 45 min on a treadmill and then intramuscularly injected with 100 μg of ovalbumin (OVA) and 200 μg of alum adjuvant. All other groups were also vaccinated at this time. Stress-VWR mice voluntarily ran on a wheel for the entire experiment. Plasma was collected before, and at 1, 2, and 4 wk postvaccination. Enzyme-linked immunosorbent assay was performed to analyze anti-OVA IgG and IgM antibodies. After 3 wk of chronic stress, all mice were injected with OVA into the ear to determine the delayed-type hypersensitivity.

Results

We found that chronic restraint stress significantly reduced body weight and caused adrenal hypertrophy. We also found both S-ECC and S-VWR groups had significantly elevated anti-OVA IgG (P < 0.05), whereas no significant differences between the two exercise groups. Neither S-ECC nor S-VWR altered anti-OVA IgM or delayed-type hypersensitivity responses compared with S-SED group.

Conclusions

Acute eccentric exercise and voluntary exercise training alleviated the chronic stress-induced anti-OVA IgG reductions in vaccination responses.
Quality of Life of asthmatic children and their caregivers
Authors: Ibrahim Nahla Khamis , Alhainiah Maha , Khayat Maie , Abulaban Orjwan , Almaghrabi Sarah , Filmban Osama
Published: March 2019

Objectives: To assess Quality of Life (QOL), and its associated factors between asthmatic children and their caregivers, and determine the correlation between QOL of patients and caregivers, at King Abdulaziz University Hospital (KAUH), Jeddah.

Methods: A cross-sectional study was conducted among eligible participants who attended Pediatric Pulmonology Outpatient Clinic of KAUH, during 2016/2017. A data collection sheet was used. The standardized Arabic version of Pediatric Asthma Quality of Life Questionnaire (PAQLQ) for children aged 7 - 17 years was completed. The caregiver who accompanied the child fulfilled the Pediatric Asthma Caregiver’s Quality of Life Questionnaire (PACQLQ). Descriptive and inferential analyses were performed.

Results: QOL scores were reduced among asthmatic children who had other type of allergy, or a family history of allergies. Uncontrolled management of asthma presented by frequent waking-up at night, frequent wheezes, visiting Emergency Rooms (ER), or hospital admission was associated with poor QOL of both asthmatic children and their caregivers. There is a positive correlation between child symptoms domain of PAQLQ and emotional domain of PACQLQ of their caregivers.

Conclusion: Uncontrolled asthma was associated with poor QOL of asthmatic child and caregivers. Better management of asthma is recommended to improve their QOL.

How to cite this:Ibrahim NK, Alhainiah M, Khayat M, Abulaban O, Almaghrabi S, Felmban O. Quality of Life of asthmatic children and their caregivers. Pak J Med Sci. 2019;35(2):521-526. doi: https://doi.org/10.12669/pjms.35.2.686

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Efficacy of a silver colloidal gel against selected oral bacteria in vitro
Authors: Tran Phat L. , Luth Keaton , Wang James , Ray Coby , de Souza Anselm , Mehta Dilip , Moeller K. W. , Moeller C. D. , Reid Ted W.
Published: March 2019

Background:It is necessary to develop new strategies to protect against bacteria such as Streptococcus mutans, Streptococcus sanguis, andStreptococcus salivarius, which contribute to tooth decay and plaque formation. Our current study investigated the efficacy of a colloidal silver gel in inhibiting biofilm formation by these principal oral bacteria, in vitro. The aim of this study was to assess the efficacy of a colloidal silver gel formulation for inhibiting bacterial biofilm formation (Ag-gel) by the principal bacteria that cause plaque formation and tooth decay.

Methods:The effect of Ag-gel on viability ofS. mutans,S. sanguis,and S. salivariuswas assessed by quantifying their colony forming units (CFU) in presence or absence of the test gel. The effect of this formulation on biofilm-forming ability of these bacteria was studied through scanning electron microscopy.

Results:Using the CFU assays, over 6 logs of inhibition (100%) were found forS. mutans,S. sanguis, andS. salivariusfor the Ag-gel-treated bacteria when compared with the control gel. In addition, the Ag-gel also inhibited biofilm formation by these three bacteria mixed together. These results were confirmed by scanning electron microscopy.

Conclusions:The Ag-gel was effective in preventing biofilm formation byS. mutans, S. sanguis, and S. salivarius. This Ag-gel should be tested for the ability to block plaque formation in the mouth, through its use as a tooth paste.
Fast and accurate differential transcript usage by testing equivalence class counts
Authors: Cmero Marek , Davidson Nadia M. , Oshlack Alicia
Published: March 2019

Background: RNA sequencing has enabled high-throughput and fine-grained quantitative analyses of the transcriptome. While differential gene expression is the most widely used application of this technology, RNA-seq data also has the resolution to infer differential transcript usage (DTU), which can elucidate the role of different transcript isoforms between experimental conditions, cell types or tissues. DTU has typically been inferred from exon-count data, which has issues with assigning reads unambiguously to counting bins, and requires alignment of reads to the genome. Recently, approaches have emerged that use transcript quantifications estimates directly for DTU. Transcript counts can be inferred from 'pseudo' or lightweight aligners, which are significantly faster than traditional genome alignment. However, recent evaluations show lower sensitivity in DTU analysis. Transcript abundances are estimated from equivalence classes (ECs), which determine the transcripts that any given read is compatible with. Recent work has proposed performing differential expression testing directly on equivalence class read counts (ECs).

Methods: Here we demonstrate that ECs can be used effectively with existing count-based methods for detecting DTU. We evaluate this approach on simulated human and drosophila data, as well as on a real dataset through subset testing.

Results: We find that ECs counts have similar sensitivity and false discovery rates as exon-level counts but can be generated in a fraction of the time through the use of pseudo-aligners.

Conclusions: We posit that equivalence class read counts are a natural unit on which to perform many types of analysis.
Trauma-informed practice
Authors: Sunderland Margot
Published: March 2019

The symptoms of ADHD, autism and other common child diagnoses often match those of childhood trauma and adverse childhood experiences. Dr Margot Sunderland explains why schools must become trauma-informed
LA CONTRIBUCIÓN DE LOS MOVIMIENTOS DE RENOVACIÓN PEDAGÓGICA EN MADRID: LA SOCIALIZACIÓN Y LA CREACIÓN DE LA IDENTIDAD DOCENTE
Authors: Parejo Llanos José Luis , Pinto José María
Published: March 2019

INTRODUCCIÓN. En este trabajo analizamos cómo los Movimientos de Renovación Pedagógica (MRP) de la Comunidad de Madrid contribuyen a crear una red de apoyo social y a la formación de la identidad profesional de los docentes miembros de los mismos. Consideramos esta como una de las aportaciones más interesantes de los MRP dentro de todo el desarrollo profesional docente que ejercen. Comenzamos el artículo realizando una pequeña aproximación a lo que son los MRP, para después centrarnos en los aspectos teóricos centrales de esta investigación: la identidad profesional y la socialización del docente. MÉTODO. Este trabajo se fundamenta en la perspectiva interpretativa-naturalista de la investigación educativa. Hemos utilizado tres técnicas e instrumentos de recogida de la información: el análisis de contenido de documentación escrita de los MRP, la observación participante a través del diario del investigador y la entrevista en profundidad a expertos temáticos. RESULTADOS. Del análisis de datos hemos comprobado cómo los MRP protegen del aislamiento docente, forjan la idea del docente que se quiere ser y se forman y organizan como grupo cohesionado, tanto de trabajo como de apoyo social y personal. Hemos podido observar cómo se crean comunidades participativas desde las cuales trabajan colaborativamente: una red social y de apoyo que se crea desde la excusa de la formación continua, por medio de la reflexión, del intercambio de ideas, de la muestra de experiencias educativas, del debate y la observación, del análisis de propuestas teóricas y prácticas. DISCUSIÓN. El trabajo conjunto de los MRP proporciona unas vivencias y un intercambio laboral que impregna la esfera social, afectiva y personal de cada sujeto participante de esta experiencia. Una influencia que refuerza y amplía las interconexiones y esta red de apoyo social y personal, la cual es básica para asegurar el amplio desarrollo profesional y la salud del docente.
Earth, Tree, Rock and Sea
Authors: Poynor Helen
Published: March 2019

The following statement of practice focuses on my experience of moving and working with others in ‘natural’ environments. The introduction contextualises this practice indicating what it can offer participants including: ‘time out’ from daily life, a deeper experience of the body and a renewed sense of kinship with the natural world. Environmental movement practice can support us to navigate our inner and outer landscapes simultaneously. The introduction is followed by two pieces of poetic writing reflecting my own experience of moving in response to two local sites with which I have a long-standing relationship: one a wooded hill-fort, the other a tidal area on the coast. The text is accompanied by images taken on the sites.
Zarf & Portakal: Dance as a medium for understanding experiences of violence
Authors: Çam Ninel
Published: March 2019

The dance performance Zarf & Portakal was staged on the 11 February 2016 at the Cemal Resit Rey Concert Hall, Istanbul. It opened a concert addressing the issue of ‘Violence against Women’, organized by the Turkish percussionist Okay Temiz. Its title is a metaphorical expression of two powerful sensations that emerged through the investigation of this subject through dance. Zarf is the Turkish word for envelope, evoked by the clothing and concealment of a woman’s body and existence. The concept of female jouissance, as used by Hélène Cixous to describe the physical, mental and spiritual aspects that come together in female sexual pleasure, is expressed through Portakal, meaning an orange, the fruit.
Politische Erziehung und politische Stabilität bei Thomas Hobbes
Authors: Brantl Dirk
Published: March 2019

Hobbes’ theory of political education and its impact on his political thought has received relatively little attention. Existing contributions rarely extend beyond Hobbes’ political philosophy to analyze how he understood education to work in the first place. This article aims to fill in the gap by first reconstructing Hobbes’ understanding of the mechanism of teaching and learning. Tracing the continuities and developments of the concept from the Elements of Law (1640) to Behemoth (1668) in the first section, the second half sketches the theory of political education and its importance to the central issue of Hobbes’ political thought, the generation of sustained political stability. The core question turns out to be: Is teaching the truth in political matters compatible with political stability? The article argues that while those who answer the question in the negative provide insufficient textual evidence, those who affirm it are hard pressed to describe a content of political education that could be politically effective.
Every Man a Legislator: Aristotle on Political Wisdom
Authors: Jagannathan Dhananjay
Published: March 2019

I argue that Aristotle’s unmodern conception of politics can only be understood by first understanding his distinctive picture of human agency and the excellence of political wisdom. I therefore undertake to consider three related puzzles: (1) why at the outset of the Nicomachean Ethics [NE] is the human good said to be the same for a city and for an individual, such that the NE’s inquiry is political? (2) why later on in the NE is political wisdom said to be the same state of soul as practical wisdom? (3) why in the Politics does Aristotle identify practical wisdom as the peculiar excellence of rulers when deliberation was said to be the common work of all citizens insofar as they are genuinely citizens? While these puzzles have individually received treatment in the literature, they have seldom been treated together. Taken independently, the passages in question can seem to express a more familiar conception of politics. In particular, each of the sameness claims made in (1) and (2) has too easily been assimilated to a more modern conception of the relation of ethics to politics and thereby domesticated. As I hope to show, in (1) Aristotle is not simply asserting that the human good in a city supervenes on the good as achieved by its inhabitants (since this by itself, while true, would fall short of establishing the political character of his inquiry in the NE); and in (2) he is not claiming only that political wisdom is a species of practical wisdom, but is rather asserting a more thoroughgoing identity between various types of deliberative excellence that are conventionally distinguished and assigned different names. Working through these passages will provide a sufficient basis for tackling (3), the question about the respective excellences of rulers and citizens. I will show that, despite his restriction of the exercise of practical wisdom to rulers, Aristotle imagines that non-ruling citizens will also exercise their political agency and thereby require a distinct rational excellence. More precisely, for Aristotle, there are two forms of political agency, deliberation on behalf of one’s community, which is perfected by practical-political wisdom, and the comprehension (sunesis) exercised by citizens on the basis of the view of life preserved by their character-virtues. Understood this way, the division of labor between rulers and citizens does not generate two spheres of activity, political and private, which could have unrelated excellences or concern distinct goods.
Uniform continuity of nonautonomous superposition operators in ΛBV-spaces
Authors: Gulgowski Jacek
Published: March 2019

In this paper we investigate the problem of uniform continuity of nonautonomous superposition operators acting between spaces of functions of bounded Λ-variation. In particular, we give the sufficient conditions for nonautonomous superposition operators to continuously map a space of functions of bounded Λ-variation into itself. The conditions cover the generators being functions of

C
1

{C^{1}}

-class (in view of two variables), but also allow for less regular functions, including discontinuous generators.
Indigoid dyes by group E monooxygenases: mechanism and biocatalysis
Authors: Heine Thomas , Großmann Carolin , Hofmann Sarah , Tischler Dirk
Published: March 2019

Since ancient times, people have been attracted by dyes and they were a symbol of power. Some of the oldest dyes are indigo and its derivative Tyrian purple, which were extracted from plants and snails, respectively. These ‘indigoid dyes’ were and still are used for coloration of textiles and as a food additive. Traditional Chinese medicine also knows indigoid dyes as pharmacologically active compounds and several studies support their effects. Further, they are interesting for future technologies like organic electronics. In these cases, especially the indigo derivatives are of interest but unfortunately hardly accessible by chemical synthesis. In recent decades, more and more enzymes have been discovered that are able to produce these indigoid dyes and therefore have gained attention from the scientific community. In this study, group E monooxygenases (styrene monooxygenase and indole monooxygenase) were used for the selective oxygenation of indole (derivatives). It was possible for the first time to show that the product of the enzymatic reaction is an epoxide. Further, we synthesized and extracted indigoid dyes and could show that there is only minor by-product formation (e.g. indirubin or isoindigo). Thus, group E monooxygenase can be an alternative biocatalyst for the biosynthesis of indigoid dyes.
Improved adherence and growth outcomes with jet-delivered growth hormone
Authors: Michaelidou Maria , Whitten Susan , Bajaj Priti , Knight Alastair , Spoudeas Helen A.
Published: March 2019

Background

We previously reported improved persistence and adherence to daily recombinant growth hormone (rGH) in children using jet transjection delivery compared to using needle-based devices. This study examines the relationship between improved adherence and medium-term growth outcomes in children receiving jet-delivered rGH (JrGH) at a single centre.

Methods

This was a retrospective longitudinal follow-up study of children (<16 years) treated with daily JrGH (somatropin; Ferring Pharmaceuticals) in the form of Zomacton® with the Zomajet® device. Delivery schedules of home distribution services were utilised to calculate adherence, quantified as the proportion of days covered (PDC) index (PDC > 0.8 adherent, PDC ≤ 0.8 less adherent). Demography, patient history, height standard deviation scores (HTSDS) and difference from mid-parental height SDS (MPHSDS − HTSDS) were extracted from hospital records for up to 3 years of treatment.

Results

Of 75 patients eligible for JrGH, 52 had PDC treatment and height data for at least 1 year and 22 for 3 years. A greater proportion of patients were classified as adherent in both 1- and 3-year treated cohorts (adherent 30 [57.7%] and 14 [63.6%], less adherent 22 [42.3%] and 8 [36.4%]). After 1 year of JrGH treatment, HTSDS was not significantly different in either adherence group. After 3 years, only adherent patients demonstrated sustained year-on-year increments in HTSDS and significant improvement in target HTSDS positions (by 1.32 SDS) compared to baseline (p = 0.0008). MPHSDS – HTSDS showed a similar significant improvement at 3 years in adherent patients only (p = 0.0043).

Conclusions

Patients adherent to JrGH demonstrate significant growth improvement compared to baseline over 3 years.
Identification of two novel TPK1 gene mutations in a Chinese patient with thiamine pyrophosphokinase deficiency undergoing whole exome sequencing
Authors: Zhu Lina , Wu Ruijuan , Ye Zhenlong , Gu Ruijie , Wang Yongxia , Hou Yu , Feng Zhichun , Ma Xiuwei
Published: March 2019

Background

The mutations of thiamine pyrophosphokinase-1 (TPK1) gene have been frequently studied in some patients with thiamine metabolism dysfunction syndrome-5 (THMD5), while TPK1 mutations in Chinese patients have been investigated by only homozygous. A search of the literature on the mutations in the Chinese population currently published revealed that no reports of compound heterozygous mutations were reported. Here, we report a Chinese patient with compound heterozygous TPK1 mutations who underwent magnetic resonance imaging (MRI), whole exome sequencing (WES), molecular diagnosis, bioinformatics analysis, and three-dimensional (3D) protein structure analysis.

Case presentation

A Chinese boy was born after an uneventful pregnancy to non-consanguineous and healthy parents. On the sixth day after his birth, the lactate level of the patient was between 8.6 mmol/L and 14.59 mmol/L in plasma (the normal level is in the range of 0.5–2.2 mmol/L). Lactate was reduced to the normal level after rehydration, acid correction, expansion, and other treatments. After 4 months, the patient presented with an acute, 3-h-long, non-induced convulsions, and was admitted to our hospital for weakness, decreased oral intake, and lethargy. Results achieved by electroencephalography (EEG), cerebrospinal fluid, and other biochemical findings were normal. A visible hemorrhagic lesion was also observed in the brain. Seizures increased significantly during infection, which was accompanied by higher lactic acid levels. MRI of the brain showed an obvious signal shadow, in which bilateral frontal and temporal parietal subarachnoid cavities were widened, and more abnormal signals were observed; therefore, further consideration of hypoxic-ischemic encephalopathy and genetic metabolic disease was taken into account.

Conclusions

The results of WES revealed that the patient was associated with compound heterozygous mutations NM_022445.3:c.[263G>A]; [226A>G] of TPK1. His parents were non-consanguineous; while his father was found to be a heterozygous carrier with the mutation c.[263G>A], his mother was identified as a heterozygous carrier with the mutation c.[226A>G]. The results indicated that the patient had a compound heterozygous TPK1 mutation, and this is the first reported case in China.
Gradient index phononic crystals and metamaterials
Authors: Jin Yabin , Djafari-Rouhani Bahram , Torrent Daniel
Published: March 2019

Phononic crystals and acoustic metamaterials are periodic structures whose effective properties can be tailored at will to achieve extreme control on wave propagation. Their refractive index is obtained from the homogenization of the infinite periodic system, but it is possible to locally change the properties of a finite crystal in such a way that it results in an effective gradient of the refractive index. In such case the propagation of waves can be accurately described by means of ray theory, and different refractive devices can be designed in the framework of wave propagation in inhomogeneous media. In this paper we review the different devices that have been studied for the control of both bulk and guided acoustic waves based on graded phononic crystals.
Exposure to environmental toxicants and young children’s cognitive and social development
Authors: Davis Alexandra N. , Carlo Gustavo , Gulseven Zehra , Palermo Francisco , Lin Chung-Ho , Nagel Susan C. , Vu Danh C. , Vo Phuc H. , Ho Thi L. , McElroy Jane A.
Published: March 2019

Background

Understanding the role of environmental toxicant exposure on children’s development is an important area of inquiry in order to better understand contextual factors that shape development and ultimately school readiness among young children. There is evidence suggesting negative links between exposure to environmental toxicants and negative physical health outcomes (i.e. asthma, allergies) in children. However, research on children’s exposure to environmental toxicants and other developmental outcomes (cognitive, socioemotional) is limited.

Objectives

The goal of the current review was to assess the existing literature on the links between environmental toxicants (excluding heavy metals) and children’s cognitive, socioemotional, and behavioral development among young children.

Methods

This literature review highlights research on environmental toxicants (i.e. pesticide exposure, bisphenol A, polycyclic aromatic hydrocarbons, tobacco smoke, polychlorinated biphenyls, flame retardants, phthalates and gas pollutions) and children’s development across multiple domains.

Results

The results highlight the potential risk of exposure to multiple environmental toxicants for young children’s cognitive and socioemotional development.

Discussion

Discussion will focus on the role of environmental toxicants in the cognitive and socioemotional development of young children, while highlighting gaps in the existing literature.