bluuebunny/crossref_metadata_2025 huggingface dataset:
Allogenic T-Cells Targeting CD123 for Adoptive Immunotherapy of Acute Myeloid Leukemia (AML)
Authors: Galetto Roman , Lebuhotel Celine , Gouble Agnes , Schiffer-Mannioui Cecile , Smith Julianne
Published: October 2019

Adoptive immunotherapy using autologous T-cells endowed with chimeric antigen receptors (CARs) has emerged as a promising new approach to treating cancer. However, a limitation of this approach is that CAR T-cells must be generated on a bespoke basis. To overcome this limitation, we have developed an allogeneic based platform for large scale production of “off-the-shelf” CAR T-cells from unrelated 3rd party donors. This platform utilizes Transcription Activator-Like Effector Nuclease (TALENTM) gene editing technology to inactivate the TCRα constant (TRAC) gene, eliminating the potential for T-cells bearing alloreactive TCR’s to mediate Graft versus Host Disease (GvHD). We have previously demonstrated that editing of the TRAC gene can be achieved at high frequencies, obtaining up to 80% of TCRαβ negative cells. This allows us to efficiently produce TCR-deficient T-cells that have been shown to no longer mediate alloreactivity in a xeno-GvHD mouse model. Furthermore, the capacity to perform efficient multiplex genome editing using TALENTM offers the possibility of simultaneously rendering cells resistant to standard chemotherapy or to tumor evasion mechanisms.

In this work we present the adaptation of this allogeneic platform to the production of T cells targeting CD123, the transmembrane alpha chain of the interleukin-3 receptor, which is expressed in tumor cells from the majority of patients with Acute Myeloid Leukemia (AML). In a first step, we have screened human primary T-cells harboring CARs with different antigen recognition domains in the context of multiple CAR architectures in order to identify candidates displaying specific activity against cell lines expressing variable levels of the CD123 antigen. To provide proof of concept for the general applicability of the allogeneic approach we have manufactured a TCR-deficient CD123 CAR T-cell (UCART123) and demonstrated that this product maintains a potent anti-tumoral activity in vitro. Experiments in an orthotopic AML mouse model using UCART123 cells are currently ongoing, in order to establish the absence of alloreactivity and the anti-tumoral activity in vivo. The ability to carry out large scale manufacturing of allogeneic, non alloreactive CD123 specific T Cells from a single healthy donor could thus offer the possibility of an off-the-shelf treatment that would be immediately available for administration to a large number of AML patients.

Disclosures

Galetto: Cellectis SA: Employment. Lebuhotel:Cellectis SA: Employment. Gouble:Cellectis SA: Employment. Schiffer-Mannioui:Cellectis SA: Employment. Smith:Cellectis SA: Employment.
Graft Versus HIV-1 Reservoir Effect after Allogeneic Stem Cell Transplantation
Authors: Kwon Mi , Nijhuis Monique , Balsalobre Pascual , Gayoso Jorge , Anguita Javier , Buno Ismael , Martinez-Laperche Carolina , Serrano David , Berenguer Juan , Miralles Pilar , Wensing Annemarie , Diez-Martin Jose Luis
Published: October 2019

Background: The use of a stem cell source homozygous for the CCR5 delta32 mutation is of particular interest in HIV+ patients in need of an allogeneic hematopoietic stem cell transplantation (SCT) given the high natural resistance against HIV-1 acquisition. In the absence of such cell source, the impact of allogeneic SCT on human immunodeficiency virus type 1 (HIV-1) reservoirs in patients receiving combination antiretroviral therapy (cART) is unknown.

Methods: Size of HIV-1 reservoirs was investigated in 3 patients with hematological malignancies receiving cART, who underwent allogeneic SCT (Table 1). Patient 1 received a myeloablative single cord blood (wild type (WT) CCR5), supported with third party HLA-mismatched CD34+ cells (haplo-cord SCT). Patients 2 and 3 underwent reduced intensity conditioning SCT of an HLA-matched sibling (heterozygous CCR5 delta32 donor and WT CCR5 donor, respectively). In-depth analysis of the HIV-1 reservoir was performed in the post-transplant period using droplet digital PCR and hemi-nested qPCR (proviral DNA copies/million PBMC). Chimerism analysis was performed by short tandem repeat PCR (STR-PCR).

Results: Proviral DNA showed a decreasing dynamics after allogeneic SCT and became undetectable in all 3 patients at 9, 18 and 1 months, respectively (Table 1). In patient 1, negativity of proviral HIV-1 DNA coincided with achievement of complete chimerism while being free of immunosuppression. Patient 2 showed undetectable proviral DNA together with the development of skin chronic GvHD. Finally, undetectable proviral DNA and complete chimerism was achieved in patient 3 early after transplantation. All patients remained in complete hematological remission.

Conclusion: All our patients showed a small HIV-1 reservoir after allogeneic SCT. The coincidence of achievement of negative proviral HIV-1 DNA and complete chimerism and/or development of GvHD suggests a role of Ògraft versus HIV-1 reservoir effectÓ in the control of HIV infection.

Disclosures

No relevant conflicts of interest to declare.
Survival in Adult Stage I Follicular Lymphoma Treated with and without Radiotherapy – a Population Based Study
Authors: Shah Binay K. , Ghimire Krishna B
Published: October 2019

Introduction:

NCCN guidelines recommend involved site radiotherapy is the preferred treatment option for Stage I follicular lymphoma. Other options include immunotherapy, immunotherapy ± chemotherapy, immunotherapy ± chemotherapy + involved site radiotherapy and observervation only. Studies have not shown overall survival benefit with one modality over other. We conducted this study to evaluate survival rate among patients who are treated with observation alone or external beam radiation.

Methods:

We selected patients with stage I follicular lymphoma diagnosed during 1992-2006 from Surveillance, Epidemiology and End Results (SEER) 18 database. We analyzed 1- and 5-years relative survival (RS) rates using SEER*stat program. We used Z test to compare relative survival rates of patients treated with (RT) or without radiotherapy (no RT) by age (>18 years, 18-60 years and >60 years) and sex.

Results:

A total of 1914 out of 5,145 adults patients with stage I follicular lymphoma diagnosed during 1992-2006 received radiotherapy. 1- and 5- year RS in patients with out vs with EBT were : 96.1 vs 100% ( Z value 6.9/ p value < 0.001) and 89.3 vs 98.7%.( Z value: 7.6/ p value < 0.001). The survival rates were significantly higher in the RT group for younger patients (1 year: 98.4 vs 100%; Z value 2.99/ p value < 0.01 and 5 year: 93.2 vs 98%; Z value 4.45/ p value < 0.001) and older patients (1 year: 94.6 vs 100%; Z value 5.8/ p value < 0.001 and 5 year: 86.5 vs 99.2%; Z value 6.21/<p value < 0.001).

Similarly 1- and 5-yr RS rates were significantly higher in the RT group compared to no RT group for all cohorts (Table 1).

Conclusion:

This study showed that relative survival rates of stage I follicular lymphoma patients receiving radiotherapy were significantly better compared to those who did not receive radiotherapy. Abstract 1317. TableSexAge in yearssurvival yearsNo External Beam RadiationExternal Beam RadiationZ value/ p valueNRelative survival ± SE %NRelative survival ± SE%Male and female≥1813,23196.10±0.401,914100.00±0.006.90/<0.001589.30±0.9098.70±0.807.61/<0.00118-6011,26398.40±0.40932100.00±0.203.00/<0.01593.20±0.9098.00±0.704.45/<0.001≥6111,96894.60 ±0.70982100.00±0.005.81/<0.001586.50±1.3099.20±1.506.21/<0.001Male≥1811,53195.50±0.70983100.00±0.006.05/<0.001587.30±1.30100.0±0.007.55/<0.001Female≥1811,70096.70±0.6093199.70±0.503.34/<0.001591.00±1.2096.20±1.302.75/<0.01Table 1: 1 year and 5 year relative survival of Follicular lymphoma stage I treated with and without external beam radiation

Disclosures

No relevant conflicts of interest to declare.
Selective occlusion of the hepatic artery and portal vein improves liver hypertrophy for staged hepatectomy
Authors: Jia Changku , Ge Ke , Xu Sunbing , Liu Ling , Weng Jie , Chen Youke
Published: October 2019

Background

To evaluate the safety and feasibility of selective occlusion of the hepatic artery and portal vein (SOAP) for staged hepatectomy (SOAPS) in patients with hepatocellular carcinoma (HCC)

Methods

From December 2014 to August 2018, 9 patients with unresectable HCC were chosen to undergo SOAPS. SOAP without liver partition was performed in the first stage. The second stage was performed when future liver remnant (FLR) was equal to or bigger than 40% of the standard liver volume (SLV). The growth rate of FLR, perioperative outcomes, and survival data was recorded.

Results

In the first stage, all the 9 patients completed SOAP. Two cases received radiological interventional method and 7 cases received open operation. None of them developed liver failure and died following SOAP. After SOAP, FLR increased 145.0 ml (115.0 to 210 ml) and 37.1% (25.6 to 51.7%) on average. The average time interval between the two stages was 14.1 days (8 to 18 days). In the second stage, no in-hospital deaths occurred after SOAPS. One patient suffered from liver failure after SOAPS, and artificial liver support was adopted and his total bilirubin level returned to normal after postoperative day 35. The alpha-fetoprotein level of 8 patients reduced to normal within 2 months after SOAPS. Among 9 patients, 5 patients survived, 4 patients died of intrahepatic recurrence, lung metastasis, or bone metastasis. In the 5 survived cases, bone metastasis and intrahepatic recurrence were found in 1 patient, intrahepatic recurrence was found in another patient, and the remaining 3 patients were free of recurrence. The median disease-free survival time and overall survival time were 10.4 and 13.9 months, respectively.

Conclusion

SOAP can facilitate rapid and sustained FLR hypertrophy, and SOAPS is safe and effective in patients with unresectable HCC.
Serum and tissue miRNAs: potential biomarkers for the diagnosis of cervical cancer
Authors: Farzanehpour Mahdieh , Mozhgani Sayed-Hamidreza , Jalilvand Somayeh , Faghihloo Ebrahim , Akhavan Setareh , Salimi Vahid , Azad Talat Mokhtari
Published: October 2019

Background

Finding new biomarkers for the early detection of cervical cancer is an essential requirement in this field. In this study, we aimed to evaluate the expression level of potential biomarkers in progression of cervical cancer in patients with cervical cancer compared to normal subjects.

Methods

The expression levels of tissue and serum miRNAs, including miR-9, miR-192 and miR-205, were investigated in 36 normal, 18 precancer, and 18 cervical cancer samples using real-time polymerase chain reaction.

Results

The results showed the higher significant expressions of miR-9, miR-192 and miR-205 in the tissue of cancer samples than those in the normal samples. Moreover, the miR-192 and miR-205 expression were significantly increased in the cancer group in comparison with the precancer group. Examination of serum samples revealed the increase in the expression level in the cancer groups than in the normal samples, for miR-9, miR-192 and miR-205 and the expressions of miR-9, miR-192 and miR-205 were significantly up-regulated in the precancer group in comparison with the normal group. Also the expression of miR-205 was remarkably increased in the cancer group in comparison with the precancer group. The receiver operating characteristic (ROC) analyses showed the highest area under the curve value for miR-192.

Conclusions

Given the increased expression level of miR-192 in cancer and in precancerous tissue and serum compared with the normal tissue and serum validated by analysing the ROC curve, miR-192 can be used as potential biomarker for the early detection of cervical cancer.
Online Social anxiety Cognitive therapy for Adolescents (OSCA): protocol for a randomised controlled trial
Authors: Leigh Eleanor , Clark David M.
Published: October 2019

Background

Adolescent social anxiety disorder (SAD) is common, impairing and persistent. There is a need to intervene early to avert its long-term consequences. Cognitive Therapy for SAD is the leading treatment for adults and shows promise for adolescents. However, given the scale of the problem of adolescent SAD and the limited availability of psychological therapists in child and adolescent mental health services, there is a substantial gap in service provision. Delivering therapy via the Internet may provide part of the solution to this problem. An Internet version of adult Cognitive Therapy for SAD has been developed, with outcomes similar to face-to-face therapy. We have recently adapted this treatment for use with adolescents with SAD. Here, we describe a randomised controlled trial designed to test the efficacy of Internet Cognitive Therapy for adolescent SAD compared to waitlist.

Methods/design

Forty adolescents aged 14–18 years with a diagnosis of SAD will be recruited via schools. Participants will be randomly allocated to Internet Cognitive Therapy or to waitlist. All participants will be assessed three times during the study—at baseline (pretreatment/wait), midtreatment/wait (week 8) and posttreatment/wait (week 15). Participants in the experimental arm will also complete weekly measures as part of the online program and they will be assessed at 3 and 6 months. Postwait, participants in the waitlist arm will be offered Internet Cognitive Therapy, and weekly and posttreatment data will also be collected for them. The trial aims to test whether Internet Cognitive Therapy is superior to waitlist in reducing social anxiety symptoms and in reducing the proportion of adolescents meeting criteria for SAD. Other outcomes of interest include depression and general anxiety symptoms. Acceptability of the online treatment will also be evaluated.

Discussion

This randomised controlled trial will provide preliminary evidence on whether this intervention, requiring relatively low levels of therapist input, is safe and clinically effective. If this is shown to be the case, Internet Cognitive Therapy for adolescents has the potential to provide a service to the large population of adolescents with untreated SAD.

Trial registration

ISRCTN Registry,ISRCTN15079139. Version 1 registered on 06/02/2019.
An electronic family health history tool to identify and manage patients at increased risk for colorectal cancer: protocol for a randomized controlled trial
Authors: Goldstein Karen M. , Fisher Deborah A. , Wu R. Ryanne , Orlando Lori A. , Coffman Cynthia J. , Grubber Janet M. , Rakhra-Burris Tejinder , Wang Virginia , Scheuner Maren T. , Sperber Nina , Datta Santanu K. , Nelson Richard E. , Strawbridge Elizabeth , Provenzale Dawn , Hauser Elizabeth R. , Voils Corrine I.
Published: October 2019

Background

Colorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3–10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, < 50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices.

Methods

In this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers’ experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective.

Discussion

This trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs.

Trial registration

ClinicalTrials.gov, NCT02247336. Registered on 25 September 2014.
Combinations of Alchornea cordifolia, Cassytha filiformis and Pterocarpus santalinoides in diarrhoegenic bacterial infections
Authors: Oli Angus Nnamdi , Obaji Monday , Enweani Ifeoma Bessie
Published: October 2019

Objectives

This study examines the rationale, if any, behind combining the extracts from the fruits of Alchornea cordifolia and Pterocarpus santalinoides and aerial parts of Cassytha filiformis in the traditional treatment of diarrhoegenic bacterial infections.

Results

Four diarrhoegenic bacterial isolates: Salmonella typhi, Shigellae dysenteriae, Escherichia coli and Staphylococcus aureus were used and their antibiotic susceptibility screening showed that they were multi-antibiotic resistant. The extracts exhibited activity against all the test isolates with minimum inhibitory concentration values ranging from 3.125 to 12.5 mg/mL. From the checkerboard assay, the fractional inhibitory concentration indices showed that C. filiformis has antagonistic and indifference activities in combination with either P. santalinoides or A. cordifolia. This showed that the combination of extracts from the fruits of A. cordifolia and P. santalinoides and aerial parts of C. filiformis is counterproductive and invalidates any claim for positive results in the management of diarrhoegenic bacterial infections.
Epigenetic synthetic lethality approaches in cancer therapy
Authors: Yang Haoshen , Cui Wei , Wang Lihui
Published: October 2019

The onset and development of malignant tumors are closely related to epigenetic modifications, and this has become a research hotspot. In recent years, a variety of epigenetic regulators have been discovered, and corresponding small molecule inhibitors have been developed, but their efficacy in solid tumors is generally poor. With the introduction of the first synthetic lethal drug (the PARP inhibitor olaparib in ovarian cancer withBRCA1mutation), research into synthetic lethality has also become a hotspot. High-throughput screening with CRISPR-Cas9 and shRNA technology has revealed a large number of synthetic lethal pairs involving epigenetic-related synthetic lethal genes, such as those encoding SWI/SNF complex subunits, PRC2 complex subunits, SETD2, KMT2C, and MLL fusion proteins. In this review, we focus on epigenetic-related synthetic lethal mechanisms, including synthetic lethality between epigenetic mutations and epigenetic inhibitors, epigenetic mutations and non-epigenetic inhibitors, and oncogene mutations and epigenetic inhibitors.
Physiological effects of high-flow oxygen in tracheostomized patients
Authors: Natalini Daniele , Grieco Domenico L. , Santantonio Maria Teresa , Mincione Lucrezia , Toni Flavia , Anzellotti Gian Marco , Eleuteri Davide , Di Giannatale Pierluigi , Antonelli Massimo , Maggiore Salvatore Maurizio
Published: October 2019

Background

High-flow oxygen therapy via nasal cannula (HFOTNASAL) increases airway pressure, ameliorates oxygenation and reduces work of breathing. High-flow oxygen can be delivered through tracheostomy (HFOTTRACHEAL), but its physiological effects have not been systematically described. We conducted a cross-over study to elucidate the effects of increasing flow rates of HFOTTRACHEAL on gas exchange, respiratory rate and endotracheal pressure and to compare lower airway pressure produced by HFOTNASAL and HFOTTRACHEAL.

Methods

Twenty-six tracheostomized patients underwent standard oxygen therapy through a conventional heat and moisture exchanger, and then HFOTTRACHEAL through a heated humidifier, with gas flow set at 10, 30 and 50 L/min. Each step lasted 30 min; gas flow sequence during HFOTTRACHEAL was randomized. In five patients, measurements were repeated during HFOTTRACHEAL before tracheostomy decannulation and immediately after during HFOTNASAL. In each step, arterial blood gases, respiratory rate, and tracheal pressure were measured.

Results

During HFOTTRACHEAL, PaO2/FiO2 ratio and tracheal expiratory pressure slightly increased proportionally to gas flow. The mean [95% confidence interval] expiratory pressure raise induced by 10-L/min increase in flow was 0.2 [0.1–0.2] cmH2O (ρ = 0.77, p < 0.001). Compared to standard oxygen, HFOTTRACHEAL limited the negative inspiratory swing in tracheal pressure; at 50 L/min, but not with other settings, HFOTTRACHEAL increased mean tracheal expiratory pressure by (mean difference [95% CI]) 0.4 [0.3–0.6] cmH2O, peak tracheal expiratory pressure by 0.4 [0.2–0.6] cmH2O, improved PaO2/FiO2 ratio by 40 [8–71] mmHg, and reduced respiratory rate by 1.9 [0.3–3.6] breaths/min without PaCO2 changes. As compared to HFOTTRACHEAL, HFOTNASAL produced higher tracheal mean and peak expiratory pressure (at 50 L/min, mean difference [95% CI]: 3 [1–5] cmH2O and 4 [1–7] cmH2O, respectively).

Conclusions

As compared to standard oxygen, 50 L/min of HFOTTRACHEAL are needed to improve oxygenation, reduce respiratory rate and provide small degree of positive airway expiratory pressure, which, however, is significantly lower than the one produced by HFOTNASAL.
Strong singularities of attractive and repulsive type to 2n-order neutral differential equation
Authors: Xin Yun , Yao Shaowen , Wang Ruichen
Published: October 2019

This paper is devoted to the existence of a positive periodic solution for a kind of 2n-order neutral differential equation with a singularity, where nonlinear term$g(t,x)$g(t,x)has strong singularities of attractive and repulsive type at the origin. Our proof is based on coincidence degree theory.
New parameterized quantum integral inequalities via η-quasiconvexity
Authors: Nwaeze Eze R. , Tameru Ana M.
Published: October 2019

We establish new quantum Hermite–Hadamard and midpoint types inequalities via a parameter $\mu \in [0,1]$
μ
∈
[
0
,
1
]
for a function F whose $|{}_{\alpha }D_{q}F|^{u}$

|

α

D
q

F
|

u

is η-quasiconvex on $[\alpha ,\beta ]$
[
α
,
β
]
with $u\geq 1$
u
≥
1
. Results obtained in this paper generalize, sharpen, and extend some results in the literature. For example, see (Noor et al. in Appl. Math. Comput. 251:675–679, 2015; Alp et al. in J. King Saud Univ., Sci. 30:193–203, 2018) and (Kunt et al. in Rev. R. Acad. Cienc. Exactas Fís. Nat., Ser. A Mat. 112:969–992, 2018). By choosing different values of μ, loads of novel estimates can be deduced. We also present some illustrative examples to show how some consequences of our results may be applied to derive more quantum inequalities.
Distribution of Modic changes in patients with low back pain and its related factors
Authors: Chen Yufeng , Bao Jie , Yan Qi , Wu Cenhao , Yang Huilin , Zou Jun
Published: October 2019

Background

To summarize the clinical distribution of Modic changes in patients with low back pain and explore the related factors.

Methods

A total of 153 patients were enrolled. Gender, age, disk degeneration, herniation, involved segments, lumbar lordosis angle, and endplate concave angle were recorded, respectively. Patients were divided into two or more groups according to a different classification. The relevant factors were studied with a multivariate logistic regression analysis to analyze their correlation.

Results

A total of 35 patients with type I changes, 110 patients with type II changes, and 8 patients with type III changes. In total, 204 disks were found with Modic changes, L1/2 (10 disks), L2/3 (18 disks), L3/4 (17 disks), L4/5 (76 disks), and L5/S1 (81 disks). Type I changes were distributed mainly under the age of 50. Multivariate regression showed that gender, age, disk degeneration, lumbar lordosis, L4/5 segment lordosis angle, and L5 lower endplate concave angle were related with different types of Modic changes. The regression equation Y = 2.410 − 1.361S − 0.633A − 0.654P + 1.106L − 0.990D (Y means type I changes, S means gender, A means age, P means disk degeneration, L means L4/5 segment lordosis angle, and D means L5 upper endplate concave angle). The OR values were S = 0.256, A = 0.531, P = 0.520, L = 3.022, D = 0.372, respectively.

Conclusions

Type II changes are the most common, followed by type I. Modic changes mostly occur in L4/5 and L5/S1; young, male, lower-grade disk degeneration, normal physiological curvature of the lumbar spine, and normal endplate concave angle were associated with type I changes; gender and lumbar curvature were the most relevant factors for different types.
Conservation issues and chemical study of the causes of alteration of a part of the Stave Church in Hopperstad (Norway)
Authors: Lehne Marit , Mantellato Sara , Aguilar Sanchez Asel Maria , Caruso Francesco
Published: October 2019

An unidentified white substance was observed on the exterior parts of the southern side of Hopperstad Stave Church, located in Vik in Sogn and Fjordane (Norway). One of the 28 remaining stave churches in the country, Hopperstad Stave Church was built between 1130 and 1150 and it constitutes an important part of Norwegian cultural heritage. Such a substance was observed for the first time in 2009 and serious concerns about its harmfulness and origin have been raised. A comprehensive study involving non-invasive (portable XRF) and micro-invasive analyses (SEM, ICP-OES, TOC) was undertaken to investigate the physico-chemical nature of this white substance. Tarring, salt migration from the nearby cemetery, atmospheric agents, leakages from the roof, biological infestation, previous treatments with pesticides are among the possible causes of the phenomenon. This work—employing a unique approach in conservation/conservation science—indicates that the white substance is mainly inorganic and crystalline. It was, therefore, possible to exclude some of the possible causes, hence, clarifying some of the conservation issues of the church.
Observed versus predicted fire behavior in an Alaskan black spruce forest ecosystem: an experimental fire case study
Authors: Drury Stacy A.
Published: October 2019

Background

Fire managers tasked with assessing the hazard and risk of wildfire in Alaska, USA, tend to have more confidence in fire behavior prediction modeling systems developed in Canada than similar systems developed in the US. In 1992, Canadian fire behavior systems were adopted for modeling fire hazard and risk in Alaska and are used by fire suppression specialists and fire planners working within the state. However, as new US-based fire behavior modeling tools are developed, Alaskan fire managers are encouraged to adopt the use of US-based systems. Few studies exist in the scientific literature that inform fire managers as to the efficacy of fire behavior modeling tools in Alaska. In this study, I provide information to aid fire managers when tasked with deciding which system for modeling fire behavior is most appropriate for their use. On the Magitchlie Creek Fire in Alaska, I systematically collected fire behavior characteristics within a black spruce (Picea mariana [Mill.] Britton, Sterns & Poggenb.) ecosystem under head fire conditions. I compared my fire behavior observations including flame length, rate of spread, and head fire intensity with fire behavior predictions from the US fire modeling system BehavePlus, and three Canadian systems: RedAPP, CanFIRE, and the Crown Fire Initiation and Spread system (CFIS).

Results

All four modeling systems produced reasonable rate of spread predictions although the Canadian systems provided predictions slightly closer to the observed fire behavior. The Canadian fire behavior prediction modeling systems RedAPP and CanFIRE provided more accurate predictions of head fire intensity and fire type than BehavePlus or CFIS.

Conclusions

The most appropriate fire behavior modeling system for use in Alaskan black spruce ecosystems depends on what type of questions are being asked. For determining the rate of fire movement across a landscape, REDapp, CanFIRE, CFIS, or BehavePlus can all be expected to provide reasonably accurate estimates of rate of spread. If fire managers are interested in using predicted flame length or energy produced for informing decisions such as which firefighting tactics will be successful, or for evaluating the ecological impacts due to burning, then the Canadian fire modeling systems outperformed BehavePlus in this case study.
Extent of disease at first cancer presentation and previous anxiety and depressive symptoms: the HUNT study
Authors: Stewart Robert , Fosså Sophie Dorothea , Hotopf Matthew , Mykletun Arnstein
Published: October 2019

Background

Depressive symptoms are associated with higher cancer mortality, whereas anxiety symptoms are associated with lower than expected risk.

Aims

This study aimed to investigate the prospective association between depressive/anxiety symptoms and the extent of disease (EOD) of first cancer at diagnosis.

Method

Prospective population-based study conducted from the second wave of the Nord-Trøndelag Health (HUNT) study. Of 65 000 residents comprehensively interviewed and examined for health status, 407 received first lifetime cancer diagnoses 1–3 years later, ascertained from the Cancer Registry of Norway, and had EOD recorded. Patients with localised disease or regional/distant spread at cancer diagnosis were analysed for earlier depressive/anxiety symptoms ascertained by the Hospital Anxiety and Depression Scale in HUNT.

Results

Beyond-local EOD was present in 59.8% of those with neither anxiety nor depression, in 76.6% of those with depression alone (odds ratio, 2.20; 1.08–4.49), in 39.3% of those with anxiety alone (odds ratio, 0.44; 0.20–0.96) and in 57.7% of those with both anxiety and depression (odds ratio, 0.92; 0.41–2.06). After adjustment for demographic and health status, and cancer type, these associations were marginally stronger, but no longer statistically significant (odds ratios, 2.26; 0.84–6.11; 0.43; 0.15–1.26; and 1.00; 0.98–1.03, respectively).

Conclusions

In people who develop cancer, beyond-local EOD at diagnosis was more common in people with previous depression and less common in people with previous anxiety; however, independence from confounding factors could not be concluded.
Multidisciplinary Cancer Management of Colorectal Cancer in Tikur Anbessa Specialized Hospital, Ethiopia
Authors: Deressa Biniyam Tefera , Cihoric Nikola , Tefesse Ephrem , Assefa Mathewos , Zemenfes Daniel
Published: October 2019

PURPOSE

Multidisciplinary cancer care is currently considered worldwide as standard for the management of patients with cancer. It improves patient diagnostic and staging accuracy and provides patients the benefit of having physicians of various specialties participating in their treatment plan. The purpose of this study was to describe the profile of patients discussed in the Tikur Anbessa Multidisciplinary Tumor Board (MTB) and the potential benefits brought by multidisciplinary care.

METHODS

The study involved the retrospective assessment of all patient cases presented to the Tikur Anbessa Hospital colorectal cancers MTB between March 2016 and November 2017. The data were collected from the MTB medical summary documents and were analyzed using SPSS version 20 (SPSS, Chicago, IL).

RESULTS

Of 147 patients with colorectal cancer, 96 (65%) were men. The median age at presentation was 46 years (range, 17-78 years). The predominant cancer was rectal (n = 101; 69%), followed by colon (n = 24; 16%). Of these, 68 (45%) and 22 (15%) had stage III and IV disease, respectively, on presentation to the MTB. The oncology department presented the majority of the patients for discussion. Most patients had undergone surgery before the MTB discussion but had no proper preoperative clinical staging information. The majority of patients with rectal cancer treated before the MTB discussion had undergone surgery upfront; however, most of the patients who were treatment naive before MTB received neoadjuvant chemoradiotherapy before surgery.

CONCLUSION

Decisions made by tumor boards are more likely to conform to evidence-based guidelines than are those made by individual clinicians. Therefore, early referral of patients to MTB before any treatment should be encouraged. Finally, other hospitals in Ethiopia should take a lesson from the Tikur Anbessa Hospital colorectal cancers MTB and adopt multidisciplinary cancer management.
Definition and Coordination of Roles and Responsibilities Among Cancer Center Clinic and Research Personnel
Authors: Craddock Lee Simon J. , Reimer Torsten , Garcia Sandra , Williams Erin L. , West Mary , Stuart Tobi , Gerber David E.
Published: October 2019

PURPOSE:

Effective enrollment and treatment of patients in cancer clinical trials require definition and coordination of roles and responsibilities among clinic and research personnel.

MATERIALS AND METHODS:

We developed a survey that incorporated modified components of the Survey of Physician Attitudes Regarding the Care of Cancer Survivors. Surveys were administered to clinic nursing staff and research personnel at a National Cancer Institute–designated comprehensive cancer center. Results were analyzed using χ2-tests, t tests, and analyses of variance.

RESULTS:

Surveys were completed by 105 staff members (n = 50 research staff, n = 55 clinic staff; 61% response rate). Research staff were more likely to feel that they had the skills to answer questions, convey information, and provide education for patients on trials (all P < .05). Both clinic and research staff reported receipt of communication about responsibilities in fewer than 30% of cases, although research staff reported provision of such information in more than 60% of cases. Among 20 tasks related to care of patients in trials, no single preferred model of responsibility assignment was selected by the majority of clinic staff for nine tasks (45%) or by research staff for three tasks (15%). Uncertainty about which team coordinates care was reported by three times as many clinic staff as research staff ( P = .01). There was also substantial variation in the preferred model for delivery of care to patients in trials ( P < .05).

CONCLUSION:

Knowledge, attitudes, and perception of care and responsibilities for patients on clinical trials differ between and among clinic and research personnel. Additional research about how these findings affect efficiency and quality of care on clinical trials is needed.
Optimizing Postprandial Glucose Management in Adults With Insulin-Requiring Diabetes: Report and Recommendations
Authors: Leahy John (Jack) L , Aleppo Grazia , Fonseca Vivian A , Garg Satish K , Hirsch Irl B , McCall Anthony L , McGill Janet B , Polonsky William H
Published: October 2019

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with type 1 and insulin-requiring type 2 diabetes: (i) the role of PPG management in reducing the risk of diabetes complications; (ii) barriers preventing effective PPG management; (iii) strategies to reduce PPG excursions and improve patient quality of life; and (iv) education and clinical tools to support endocrinologists in improving PPG management. We concluded that managing PPG to minimize or prevent diabetes-related complications will require elucidating fundamental questions about optimal ways to quantify and clinically assess the metabolic dysregulation and consequences of the abnormal postprandial state in diabetes and recommend research strategies to address these questions. We also identified practical strategies and tools that are already available to reduce barriers to effective PPG management, optimize use of new and emerging clinical tools, and improve patient self-management and quality of life.
From Sanctuary to Safe Space
Authors: Ellison Treva
Published: October 2019

This article focuses on how the trajectories of gay and lesbian police-reform efforts in Los Angeles model a transition from a politics of sanctuary to the production of safe space. The production of safe space is conditioned by the multiplication of discourses of race, gender, and sexuality emblematized by the rise of identity-based neighborhood politics throughout the postwar period, and how these politics interface with the reterritorialization of the welfare state and the advent of community policing. The article historicizes several Stonewall-era gay organizations, showing how activists enacted a politics of sanctuary that helped to decriminalize gay and lesbian identity, and then arguing that this politics of sanctuary was drawn into the production of safe space. This writing invites possibilities for abolitionist organizing by demonstrating the life cycle of law and order that circumscribes urban, identity-based, antiviolence, and neighborhood-based politics.
Sanctuary Squats
Authors: Hung Carla
Published: October 2019

This article details the political contestations of refugee occupiers after they were violently evicted from their home, colloquially called Piazza Indipendenza. Participant observation as a friend of the Eritrean refugees who occupied Piazza Indipendenza during the time of their eviction brought to light the way refugee occupiers both demand rights to subsidized housing and care for each other. Refugees confront the discriminatory distribution of integration resources in Italy by establishing autonomous structures, like housing occupations of abandoned buildings, to both approximate their entitlement to subsidized housing and assert their rights. For many Eritrean refugee occupiers in Rome, it is the Habesha community itself that provides the most reliable form of care, shelter, and protection, such that migrant-occupied housing projects (squats) act as sites of sanctuary. Sanctuary squats act as shelters from which to contest repressive governmental policies.
Freedom to Move, Freedom to Stay, Freedom to Return
Authors: Maira Sunaina
Published: October 2019

This article focuses on the sanctuary movement in the United States and Europe, putting into conversation with one another migrant solidarity activists from different national contexts. This transnational roundtable draws on interviews with activists in the San Francisco Bay Area as well as in the United Kingdom and Switzerland, and on a workshop on sanctuary activism that involved forty activists from the Bay Area, Europe, and Australia. The article explores the meaning of sanctuary in these different locations and the strategies used by activists to create various forms of sanctuary while grappling with its contradictions. It addresses three key themes: (1) the meaning of sanctuary in campaigns that enact the right to freedom of movement across borders; (2) the binary of “good”/deserving versus “bad”/unworthy migrants; and (3) an abolitionist sanctuary model that links border violence to carcerality, neoliberal capitalism, white supremacy, settler colonialism, and fascism.
Elimination Politics
Authors: Feldman Ilana
Published: October 2019

Focusing on punishment and imprisonment across three time periods, this essay explores the two-pronged attack on Palestinian politics that has characterized the settler-colonial project in Palestine over the past one hundred years. This double move entails an attempt to deny or destroy Palestinian political community, while simultaneously identifying Palestinians as political actors, specifically as bad actors. The aim is to undermine Palestinian political capacity by disrupting connection and organizing, while still deploying the weapon of categorizing Palestinians, individually and collectively, as enemies—under labels such as insurgents, terrorists, and enemy combatants. The struggle over elimination in Palestine has continued through multiple changes in governing regime and across territorial reconfigurations. The different tactics deployed against Palestinians over these decades are a product both of these changes and of the continuing Palestinian refusal to acquiesce to their elimination.
Disruption of the pancreatic vasculature in zebrafish affects islet architecture and function
Authors: Mullapudi Sri Teja , Boezio Giulia L. M. , Rossi Andrea , Marass Michele , Matsuoka Ryota L. , Matsuda Hiroki , Helker Christian S. M. , Yang Yu Hsuan Carol , Stainier Didier Y. R.
Published: October 2019

A dense local vascular network is crucial for pancreatic endocrine cells to sense metabolites and secrete hormones, and understanding the interactions between the vasculature and the islets may allow for therapeutic modulation in disease conditions. Using live imaging in two models of vascular disruption in zebrafish, we identified two distinct roles for the pancreatic vasculature. At larval stages, expression of a dominant negative version of Vegfaa (dnVegfaa) in β-cells led to vascular and endocrine cell disruption with a minor impairment in β-cell function. In contrast, expression of a soluble isoform of Vegf receptor 1 (sFlt1) in β-cells blocked the formation of the pancreatic vasculature and drastically stunted glucose response while islet architecture was not affected. Notably, these effects of dnVegfaa or sFlt1 were not observed in animals lacking vegfaa, vegfab, kdrl, kdr, or flt1 function, indicating that they interfere with multiple ligands and/or receptors. In adults, disrupted islet architecture persisted in dnVegfaa expressing animals, while sFlt1 expressing animals displayed large sheets of β-cells along their pancreatic ducts, accompanied by impaired glucose tolerance in both models. Thus, our study reveals novel roles for the vasculature in patterning and function of the islet.
Regulation of nuclear-cytoplasmic partitioning by thelin-28-lin-46pathway reinforces microRNA repression of HBL-1 to confer robust cell-fate progression inC. elegans
Authors: Ilbay Orkan , Ambros Victor
Published: October 2019

MicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. In C. elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2) stage cell-fates, and the let-7-family microRNAs temporally down-regulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel to let-7-family microRNAs, the conserved RNA binding protein LIN-28 and its downstream gene lin-46, also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how the lin-28-lin-46 pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by the lin-28-lin-46 pathway is independent of the let-7/lin-4 microRNA complementary sites (LCSs) in the hbl-1 3'UTR, and involves a stage-specific post-translational regulation of HBL-1 nuclear accumulation. We find that LIN-46 is necessary and sufficient to prevent nuclear accumulation of HBL-1. Our results illuminate that the robust progression from L2 to L3 cell-fates depends on the combination of two distinct modes of HBL-1 down-regulation: decreased synthesis of HBL-1 via let-7-family microRNA activity, and decreased nuclear accumulation of HBL-1 via action of the lin-28-lin-46 pathway.
Compression Garments Reduce Muscle Movement and Activation during Submaximal Running
Authors: BROATCH JAMES R. , BROPHY-WILLIAMS NED , PHILLIPS ELISSA J. , O’BRYAN STEVEN J. , HALSON SHONA L. , BARNES SHANNON , BISHOP DAVID J.
Published: October 2019

Purpose

The purpose of this study was to investigate the effectiveness of sports compression tights in reducing muscle movement and activation during running.

Methods

A total of 27 recreationally active males were recruited across two separate studies. For study 1, 13 participants (mean ± SD = 84.1 ± 9.4 kg, 22 ± 3 yr) completed two 4-min treadmill running bouts (2 min at 12 and 15 km·h−1) under two conditions: a no-compression control (CON1) and compression (COMP). For study 2, 14 participants (77.8 ± 8.4 kg, 27 ± 5 yr) completed four 9-min treadmill running bouts (3 min at 8, 10, and 12 km·h−1) under four conditions: a no-compression control (CON2) and three different commercially available compression tights (2XU, Nike, and Under Armor). Using Vicon 3D motion capture technology, lower limb muscle displacement was investigated in both study 1 (thigh and calf) and study 2 (vastus lateralis + medialis [VAS]; lateral + medial gastrocnemius [GAS]). In addition, study 2 investigated the effects of compression on soft tissue vibrations (root-mean-square of resultant acceleration, RMS A
r), muscle activation (iEMG), and running economy (oxygen consumption, V˙O2) during treadmill running.

Results

Wearing compression during treadmill running reduced thigh and calf muscle displacement as compared with no compression (both studies), which was evident across all running speeds. Compression also reduced RMS A
r and iEMG during treadmill running, but it had no effect on running economy (study 2).

Conclusion

Lower limb compression garments are effective in reducing muscle displacement, soft tissue vibrations, and muscle activation associated with the impact forces experienced during running.
Interventional radiology training: a comparison of 5 English-speaking countries
Authors: Mandal Indrajeet , Minocha Amal , Yeung Jason , Bandula Steve , Rabouhans Jeremy
Published: October 2019

Objective:

To compare key characteristics of interventional radiology (IR) training in the UK with four other English-speaking countries (USA, Canada, Australia and New Zealand) and summarise requirements for training.

Methods:

Main features examined were career pathway and requirements, examinations required, specific competition for IR and the process of applying for training as an international medical graduate. Data were collected from official governing body publications, literature and personal experience.

Results:

Several differences were highlighted, including length of training (ranging from 6 to 9 years after medical school), length of IR-specific training (ranging from 1 to 3 years) and examinations required (USA and Canada have additional IR-specific examinations). The level of competition is generally high, in all countries.

Conclusions:

With the demand for IR services set to increase over the next few years, it is crucial that more IR specialists are trained to meet this demand. Awareness of training structures in other countries can highlight opportunity and pitfalls, and help ensure the number of highly trained interventional radiologists in the UK continues to grow.