bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Cyclization, and Cytotoxic Activity of 2,3-Secolupane Triterpenoids With an Ethylketone Fragment
Authors: Konysheva Anastasia V. , Eroshenko Daria V. , Grishko Victoria V.
Published: October 2019

3-Ethyl substituted triterpenoids with a fragmented and 5-membered A ring were synthesized from the lupane ketoxime via the Beckmann reaction and intramolecular oxonitrile cyclization, respectively. Transformations of the triterpenic isopropylidene fragment with the formation of C(30) and C(20) modified derivatives were performed by either allylic C(30) oxidation or ozonolytic cleavage of the C(20)-C(29) double bond. Antitumor activity of the synthesized compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,3-diphenyl-tetrazolium bromide test against 7 human cancer cell lines. Methyl 1-cyano-3-ethyl-3-oxo-2,3-seco-2-norlup-20(29)-en-30-al-28-oate (4), methyl 3-[1-bromoethyl]-1-cyano-3-oxo-2,3-seco-2-norlup-20(29)-en-30-al-28-oate (6), and methyl 1-cyano-3-ethyl-2-norlup-1(3),20(29)-dien-30-al-28-oate (9) were selected as compounds with highest cytotoxicity (IC50 1.38-15.91 μM).
ANGPTL2 Promotes Inflammation via Integrin α5β1 in Chondrocytes
Authors: Takano Mami , Hirose Naoto , Sumi Chikako , Yanoshita Makoto , Nishiyama Sayuri , Onishi Azusa , Asakawa Yuki , Tanimoto Kotaro
Published: October 2019

Background

Angiopoietin-like protein 2 (ANGPTL2) is a secreted molecule with numerous physiologic and pathologic functions, for example, in angiogenesis, hematopoiesis, and tumorigenesis. Although recent studies implicated ANGPTL2 in chronic inflammation in mouse peritoneal macrophages, human ligamentum flavum fibroblasts, and human retinal microvascular endothelial cells, the mechanism underlying ANGPTL2-associated inflammation in chondrocytes remains unclear. Therefore, it was investigated whether ANGPTL2 is expressed in or functions in chondrocytes.

Methods

Expression of ANGPTL2 and its receptor, integrin α5β1 were examined over time in ATDC5 cells using real-time RT-PCR (reverse transcription–polymerase chain reaction) analysis. ATDC5 cells were then incubated with or without ANGPTL2 for 3 hours, and expression of the IL-1β, TNF-α, COX-2, aggrecanase (ADAMTS)-5, matrix metalloproteinase (MMP)-3, and MMP-13 genes were examined using real-time RT-PCR. Additionally, phosphorylation of ERK, JNK, p38, Akt, and NF-κB was examined by western blotting. Furthermore, it was also investigated for the effect of anti-integrin α5β1 antibody on the expression of inflammatory markers and intracellular signaling pathways.

Results

ANGPTL2 induced the phosphorylation of all 3 MAPKs, Akt, and NF-κB and dramatically upregulated the expression of inflammation-related factor genes. Inhibiting the activation of integrin α5β1 suppressed these reactions.

Conclusion

ANGPTL2 may induce inflammatory factors by stimulating the integrin α5β1/MAPKs, Akt, and NF-κB signaling pathway.
Keys to early diagnosis of cardiac amyloidosis: red flags from clinical, laboratory and imaging findings
Authors: Vergaro Giuseppe , Aimo Alberto , Barison Andrea , Genovesi Dario , Buda Gabriele , Passino Claudio , Emdin Michele
Published: October 2019

Cardiac involvement in systemic amyloidosis, due either to immunoglobulin light-chain or transthyretin amyloidosis, influences clinical presentation and is a strong predictor of unfavourable outcome. Until recently considered as a rare, incurable disease, cardiac amyloidosis, is still mis/underdiagnosed, although treatments effective in improving patient survival are now available for both subtypes, including chemotherapy regimens for immunoglobulin light-chain amyloidosis and tetramer stabiliser for transthyretin amyloidosis. Achieving a timely diagnosis allows initiating life-saving therapies and requires the early recognition of clinical, laboratory and imaging signs of cardiac involvement, some of them may be apparent well before the disease becomes clinically manifest. Given the systemic nature of amyloidosis, a close interaction among experts in multiple specialties is also required, including cardiologists, nephrologists, haematologists, neurologists, radiologists, nuclear medicine specialists and internists. As an increased awareness about disease presentation is required to ameliorate diagnostic performance, we aim to provide the clinician with a guide to the screening and early diagnosis of cardiac amyloidosis, and to review the clinical, biohumoral and instrumental ‘red flags’ that should raise the suspicion of cardiac amyloidosis.
Sacubitril-valsartan versus enalapril for acute decompensated heart failure: a cost-effectiveness analysis
Authors: Perera Kanila , Ademi Zanfina , Liew Danny , Zomer Ella
Published: October 2019

Background

The Comparison of Sacubitril–Valsartan versus Enalapril on Effect on NT-proBNP in Patients Stabilised from an Acute Heart Failure Episode (PIONEER-HF) trial demonstrated significant reductions in N-terminal pro-B-type natriuretic peptide. Our study explored the cost-effectiveness of the use of sacubitril-valsartan versus enalapril in acute decompensated heart failure from the Australian healthcare perspective.

Methods

A Markov model was designed using data from the PIONEER-HF trial to model the clinical progress and costs of patients over a lifetime time horizon. The model consisted of three health states: ‘alive and event-free’, ‘alive after non-fatal hospitalisation for acute decompensated heart failure’ or ‘dead’. Costs and utilities were estimated from published sources. The cost of sacubitril-valsartan (per the Australian pharmaceutical benefits schedule) was AU$7.08/day. Outcomes of interest were the incremental cost-effectiveness ratios in terms of cost per quality-adjusted life year gained and cost per year of life saved. Cost and benefits were discounted at 5.0% per annum.

Results

Compared to enalapril, sacubitril-valsartan was estimated to cost an additional AU$7464 (discounted) per person, but lead to 0.127 years of life saved (discounted) and 0.096 quality-adjusted life years gained (discounted) over a lifetime analysis. These equated to incremental cost-effectiveness ratios of AU$58,629/year of life saved (US$41,795, EU€58,629, GBP£32,001) and AU$77,889/quality-adjusted life year gained (US$55,526, EU€49,202, GBP£42,504). We have assumed a threshold of AU$50,000/quality-adjusted life year gained to suggest cost-effectiveness.

Conclusions

At its current acquisition price, sacubitril-valsartan in comparison to enalapril is not likely to be cost-effective in the management of acute decompensated heart failure in Australia. A price reduction of more than 25% would confer cost-effectiveness.
No effects of a long-term physical activity intervention on executive functioning among adolescents
Authors: Sjöwall Douglas , Thorell Lisa B , Mandic Mirko , Westerståhl Maria
Published: October 2019

Objectives:

We investigated whether a school-based physical activity intervention would lead to improvements in working memory, inhibition and cognitive flexibility in adolescents aged 13–15 years.

Methods:

The adolescents at the active school ( n = 108) participated in an intervention that included increased physical activity for 20 min/day, focused on aerobic activity with low cognitive demands for an entire school year. The adolescents at the control school ( n = 59) received no extra physical activity. At the beginning (baseline) and end (follow-up) of the school year, the participants performed tests of executive function (working memory, inhibition and cognitive flexibility) and performed tests of physical fitness and health.

Results:

There was no change in executive functioning at follow-up when comparing the schools. However, only 46% complied with the intervention. When non-compliers were excluded from the analyses, the results remained the same, except for a small but significant increase in working memory for the active school as compared to the control school.

Conclusion:

These results indicate that compliance with the intervention was low and that aerobic exercise with low cognitive load does not produce improvements in executive functioning.
Patient Knowledge of Correct Dosage Regimen; The Need for Good Dispensing Practice
Authors: Gudeta Tadesse , Mechal Dinku
Published: October 2019

Background: The inappropriate use of medicine is a widespread problem, especially in developing countries. Proper dispensing practices as part of medication therapy increase benefits and minimize risks to the consumers. Objective: The purpose of this study was to assess patient knowledge of dosage regimen and the pharmacists dispensing practice. Method: A cross-sectional study design was conducted at Jimma Medical Center from March 1, 2018 to April 29, 2018. Data were collected prospectively using checklists and structured questionnaires. Results: Of the total prescribed drugs, 689 (74.25%) were actually dispensed, and 239 (34.7%) drugs were adequately labeled. The average dispensing and consultation times were 41.45 ± 12.1 and 49.13 ± 12 seconds, respectively. Of the total participants on exit interview, 267 (74.8%) correctly reported the dosage schedule of dispensed medicines. From the multivariate logistics regression analysis, language barrier (adjusted odds ratio [AOR] = 32.6, 95% confidence interval [CI] = 12.23-87.15), severity of health condition (AOR = 7.3, 95% CI = 2.70-19.56), and the number of drugs dispensed (AOR = 0.41, 95% CI = 0.18-0.87 [1 drug], AOR = 0.16, 95% CI = 0.61-0.42 [2 drugs]) have shown significant association with patient knowledge of dosage regimen. Conclusions: Majority of the patients did not receive the prescribed medicines from the outpatient pharmacy of Jimma Medical Center. Plus, only a few of the dispensed drugs contain all the necessary information. However, a large portion of the participants correctly reported the dosage schedule of their drugs.
Sexualization of Girls: Addressing Criticism of the APA Report, Presenting New Evidence
Authors: Lamb Sharon , Koven Julie
Published: October 2019

The Report of the APA Task Force on the Sexualization of Girls, published in 2007, is one of the most frequently accessed APA reports. The task force was formed and report was compiled in response to concerns regarding the impact of sexualization on girls and society at large. This article presents a review of research published since the report was released to examine the continued presence and impact of sexualizing material. In addition, we review the new evidence in light of critiques of the report that followed its publication. Finally, we present emerging ideas regarding prevention and interventions. While general findings of the original report hold true, and some criticisms have been addressed, the present review suggests the need for more research on childhood, rather than adolescents and adults, and more research using samples that have gender, sexuality, racial, and ethnic diversity.
Where Are All the Reading Teachers? Redesigning a Reading Master’s Degree
Authors: Dahle-Huff Kari L. , Waller Rachael J.
Published: October 2019

This article examines how a small, regional comprehensive university located in a geographically isolated context reinvigorated its master’s degree in reading. The process began with articulating a vision for the program that was centered in understanding the unique geographic context of the region. Coherent program goals were then developed to align with state and national standards. Following goal development, curriculum was developed which addressed methods of teaching reading grounded in rich theoretical underpinnings. This article will also address how partnerships with K–12 stakeholders helped shape the curriculum redesign. Finally, this article also addresses how quality online pedagogies bridge relationships across rural regions and ultimately helps to bring research-based interventions to children across the state.
Mineralogy and genesis of pyrochlore apatitite from The Good Hope Carbonatite, Ontario: A potential niobium deposit
Authors: Mitchell Roger H. , Wahl Rudy , Cohen Anthony
Published: October 2019

The Good Hope carbonatite is located adjacent to the Prairie Lake alkaline rock and carbonatite complex in northwestern Ontario. The occurrence is a heterolithic breccia consisting of diverse calcite, dolomite and ferrodolomite carbonatites containing clasts of magnesio-arfvedsonite + potassium feldspar, phlogopite + potassium feldspar together with pyrochlore-bearing apatitite clasts. The apatitite occurs as angular, boudinaged and schlieren clasts up to 5 cm in maximum dimensions. In these pyrochlore occurs principally as euhedral single crystals (0.1–1.5 cm) and can comprise up to 25 vol.% of the clasts. Individual clasts contain compositionally- and texturally-distinct suites of pyrochlore. The pyrochlores are hosted by small prismatic crystals of apatite (~100–500 μm × 10–25 μm) that are commonly flow-aligned and in some instances occur as folds. Allotriogranular cumulate textures are not evident in the apatitites. The fluorapatite does not exhibit compositional zonation under back-scattered electron spectroscopy, although ultraviolet and cathodoluminescence imagery shows distinct cores with thin (<50 μm) overgrowths. Apatite lacks fluid or solid inclusions of other minerals. The apatite is rich in Sr (7030–13,000 ppm) and rare earth elements and exhibits depletions in La, Ce, Pr and Nd (La/NdCN ratios (0.73–1.14) relative to apatite in cumulate apatitites (La/NdCN > 1.5) in the adjacent Prairie Lake complex. The pyrochlore are primarily Na–Ca pyrochlore of relatively uniform composition and minor Sr contents (<2 wt.% SrO). Irregular resorbed cores of some pyrochlores are A-site deficient (>50%) and enriched in Sr (6–10 wt.% SrO), BaO (0.5–3.5 wt.%), Ta2O5 (1–2 wt.%) and UO2 (0.5–2 wt.%). Many of the pyrochlores exhibit oscillatory zoning. Experimental data on the phase relationships of haplocarbonatite melts predicts the formation of apatite and pyrochlore as the initial liquidus phases in such systems. However, the texture of the clasts indicates that pyrochlore and apatite did not crystallise together and it is concluded that pyrochlores formed in one magma have been mechanically mixed with a different apatite-rich magma. Segregation of the apatite–pyrochlore assemblage followed by lithification resulted in the apatitites, which were disrupted and fragmented by subsequent batches of diverse carbonatites. The genesis of the pyrochlore apatitites is considered to be a process of magma mixing and not simple in situ crystallisation.
Identification of a tumor-specific allo-HLA–restricted γδTCR
Authors: Kierkels G. J. J. , Scheper W. , Meringa A. D. , Johanna I. , Beringer D. X. , Janssen A. , Schiffler M. , Aarts-Riemens T. , Kramer L. , Straetemans T. , Heijhuurs S. , Leusen J. H. W. , San José E. , Fuchs K. , Griffioen M. , Falkenburg J. H. , Bongiovanni L. , de Bruin A. , Vargas-Diaz D. , Altelaar M. , Heck A. J. R. , Shultz L. D. , Ishikawa F. , Nishimura M. I. , Sebestyén Z. , Kuball J.
Published: October 2019

Key Points

We describe a novel allo-tumor–reactive and CD8α-dependent Vγ5Vδ1TCR. The molecular interface with proximity to the peptide-binding groove of HLA-A*24:02 is an essential determinant of recognition.
Delignification of softwood by glycerol from biodiesel by-product I: model reaction using glycerol and fatty acid sodium soap mixture for pretreatment on bioethanol production
Authors: Todaka Masatoshi , Kowhakul Wasana , Masamoto Hiroshi , Shigematsu Mikiji
Published: October 2019

This study investigated the use of glycerol–fatty acid sodium soap mixtures to delignify woody biomass as a model for utilization of crude glycerol by-product from biodiesel manufacture. Lignin-bearing glycerol was also produced. Delignification was carried out using glycerol mixed with sodium salts of laurate, stearate, oleate, or linoleate at 100–250 °C for 0.5–3 h. Oak, beech, bamboo, and rice straw were easily delignified by 20% sodium oleate dissolved in glycerol at around 150 °C for 1 h. For softwood (Japanese cedar and spruce), delignification did not occur below 200 °C. However, the lignin content decreased from 37.5% in untreated Japanese cedar to 10.6% and from 29.4% in untreated spruce to 11.2% by treatment at 250 °C. Japanese cedar was not delignified in glycerol mixtures with oleic acid or sodium acetate. It is suggested that the surfactant activity of soap assists delignification, but the alkaline action of sodium acetate was not effective. Enzymatic saccharification of delignified Japanese cedar (9.3% lignin) and oak (3.6% lignin) samples gave glucose yields of 0.55–0.67 g/g after 72 h and these yields were comparable with that from pure cellulose (0.77 g/g). Lignin dissolution also increased the calorific value of the collected glycerol fraction from 20 to 25 MJ/kg. The results suggest that a waste-free delignification method can be achieved based on the combined processes of biodiesel and bioethanol production.
Can quality improvement improve the quality of care? A systematic review of reported effects and methodological rigor in plan-do-study-act projects
Authors: Knudsen Søren Valgreen , Laursen Henrik Vitus Bering , Johnsen Søren Paaske , Bartels Paul Daniel , Ehlers Lars Holger , Mainz Jan
Published: October 2019

Background

The Plan-Do-Study-Act (PDSA) method is widely used in quality improvement (QI) strategies. However, previous studies have indicated that methodological problems are frequent in PDSA-based QI projects. Furthermore, it has been difficult to establish an association between the use of PDSA and improvements in clinical practices and patient outcomes. The aim of this systematic review was to examine whether recently published PDSA-based QI projects show self-reported effects and are conducted according to key features of the method.

Methods

A systematic literature search was performed in the PubMed, Embase and CINAHL databases. QI projects using PDSA published in peer-reviewed journals in 2015 and 2016 were included. Projects were assessed to determine the reported effects and the use of the following key methodological features; iterative cyclic method, continuous data collection, small-scale testing and use of a theoretical rationale.

Results

Of the 120 QI projects included, almost all reported improvement (98%). However, only 32 (27%) described a specific, quantitative aim and reached it. A total of 72 projects (60%) documented PDSA cycles sufficiently for inclusion in a full analysis of key features. Of these only three (4%) adhered to all four key methodological features.

Conclusion

Even though a majority of the QI projects reported improvements, the widespread challenges with low adherence to key methodological features in the individual projects pose a challenge for the legitimacy of PDSA-based QI. This review indicates that there is a continued need for improvement in quality improvement methodology.
Isolating phyllotactic patterns embedded in the secondary growth of sweet cherry (Prunus avium L.) using magnetic resonance imaging
Authors: Eithun Mitchell , Larson James , Lang Gregory , Chitwood Daniel H. , Munch Elizabeth
Published: October 2019

Background

Epicormic branches arise from dormant buds patterned during the growth of previous years. Dormant epicormic buds remain just below the surface of trees, pushed outward from the pith during secondary growth, but maintain vascular connections. Epicormic buds can be activated to elongate into a new shoot, either through natural processes or horticultural intervention, to potentially rejuvenate orchards and restructure tree architecture. Because epicormic structures are embedded within secondary growth, tomographic approaches are a useful method to study them and understand their development.

Results

We apply techniques from image processing to determine the locations of epicormic vascular traces embedded within secondary growth of sweet cherry (Prunus avium L.), revealing the juvenile phyllotactic pattern in the trunk of an adult tree. Techniques include the flood fill algorithm to find the pith of the tree, edge detection to approximate the radius, and a conversion to polar coordinates to threshold and segment phyllotactic features. Intensity values from magnetic resonance imaging (MRI) of the trunk are projected onto the surface of a perfect cylinder to find the locations of traces in the “boundary image”. Mathematical phyllotaxy provides a means to capture the patterns in the boundary image by modeling phyllotactic parameters. Our cherry tree specimen has the conspicuous parastichy pair (2,3), phyllotactic fraction 2/5, and divergence angle of approximately 143°.

Conclusions

The methods described provide a framework not only for studying phyllotaxy, but also for processing of volumetric image data in plants. Our results have practical implications for orchard rejuvenation and directed approaches to influence tree architecture. The study of epicormic structures, which are hidden within secondary growth, using tomographic methods also opens the possibility of studying genetic and environmental influences such structures.
Prospective intra/inter-observer evaluation of pre-brachytherapy cervical cancer tumor width measured in TRUS and MR imaging
Authors: Federico Mario , Hernandez-Socorro Carmen Rosa , Ribeiro Ivone , Martin Jesus Gonzalez , Oramas Maria Dolores Rey-Baltar , Saez-Bravo Marta Lloret , Jimenez Pedro Carlos Lara
Published: October 2019

Background

Ultrasound (US) imaging has been proved as an excellent diagnostic tool in gynecology and, due to its wide availability and limited cost, is under intense investigation as base for dose adaptation in cervical cancer brachytherapy. Purpose of this work is to test inter/intra-observer uncertainties between magnetic resonance (MR) and trans-rectal ultrasound (TRUS) imaging in defining maximum tumor width before first brachytherapy (BT) application in a prospective cohort of cervical cancer patients undergoing image-guided adaptive brachytherapy (IGABT).

Methods

One hundred ten consecutive cervical cancer patients treated between 2013 and 2016 were included. Before the first BT implant patients underwent MR and TRUS scan with no applicator in place. Images were independently analyzed by three examiners, blinded to the other’s results. With clinical information at hand, maximum tumor width was measured on preBT TRUS and MR. Quantitative agreement analysis was undertaken. Intra-class correlation coefficient (ICC), Passing-Bablok and Bland Altman plots were used to evaluate the intra/inter-observers measurement agreement.

Results

Average difference between tumor width measured on MR (HRCTVMR) and TRUS (HRCTVTRUS) was 1.3 ± 3.2 mm (p <  0.001); 1.1 ± 4.6 mm (p = 0.01) and 0.7 ± 3 mm (p = 0.01). The error was less than 3 mm in 79, 82 and 80% of the measurements for the three observers, respectively. Intra-observer ICC was 0.96 (CI95% 0.94–0.97), 0.93 (CI95% 0.9–0.95) and 0.96 (CI95% 0.95–0.98) respectively. Inter-observer ICC for HRCTVMR width measures was 0.92 (CI95% 0.89–0.94) with no difference among FIGO stages. Inter-observer ICC for HRCTVTRUS was 0.86 (CI95% 0.81–0.9). For FIGO stage I and II tumors, ICC HRCTVTRUS values were comparable to respective HRCTVMR ICC values. For larger tumors HRCTVTRUS inter-observer ICC values were lower than respective HRCTVMR although remaining acceptable.

Conclusions

Our results suggest that TRUS is equivalent to MR in assessing preBT tumor maximum width in cervical cancer FIGO stage I/II. In more advanced stages TRUS seems to be slightly inferior to MR although maintaining a good agreement to gold standard imaging.
Urocortins in the mammalian endocrine system
Authors: Squillacioti Caterina , Pelagalli Alessandra , Liguori Giovanna , Mirabella Nicola
Published: October 2019

Urocortins (Ucns), peptides belonging to the corticotropin-releasing hormone (CRH) family, are classified into Ucn1, Ucn2, and Ucn3. They are involved in regulating several body functions by binding to two G protein-coupled receptors: receptor type 1 (CRHR1) and type 2 (CRHR2). In this review, we provide a historical overview of research on Ucns and their receptors in the mammalian endocrine system. Although the literature on the topic is limited, we focused our attention particularly on the main role of Ucns and their receptors in regulating the hypothalamic–pituitary–adrenal and thyroid axes, reproductive organs, pancreas, gastrointestinal tract, and other tissues characterized by “diffuse” endocrine cells in mammals. The prominent function of these peptides in health conditions led us to also hypothesize an action of Ucn agonists/antagonists in stress and in various diseases with its critical consequences on behavior and physiology. The potential role of the urocortinergic system is an intriguing topic that deserves further in-depth investigations to develop novel strategies for preventing stress-related conditions and treating endocrine diseases.
Reducing Asthma Attacks in Children using Exhaled Nitric Oxide as a biomarker to inform treatment strategy: a randomised trial (RAACENO)
Authors: Turner S. , Cotton S. C. , Emele C. D. , Thomas R. , Fielding S. , Gaillard E. A. , de Jongste J. C. , Morgan H. , Neilson A. R. , Norrie J. , Pijnenburg M. , Price D. , Thomas M.
Published: October 2019

Background

Childhood asthma is a common condition. Currently there is no validated objective test which can be used to guide asthma treatment in children. This study tests the hypothesis that the addition of fractional exhaled nitric oxide (FENO) monitoring in addition to standard care reduces the number of exacerbations (or attacks) in children with asthma.

Methods

This is a multi-centre, randomised controlled study. Children will be included of age 6–16 years who have a diagnosis of asthma, currently use inhaled corticosteroids (ICSs) and have had an exacerbation in the previous 12 months. Exclusion criteria include being unable to provide FENO measurement at baseline assessment, having another chronic respiratory condition and being currently treated with maintenance oral steroids. Participants will be recruited in both primary and secondary care settings and will be randomised to either receive asthma treatment guided by FENO plus symptoms (FENO group) or asthma treatment guided by symptoms only (standard care group). Within the FENO group, different treatment decisions will be made dependent on changes in FENO. Participants will attend assessments 3, 6, 9 and 12 months post randomisation. The primary outcome is asthma exacerbation requiring prescription and/or use of an oral corticosteroid over 12 months as recorded by the participant/parent or in general practitioner records. Secondary outcomes include time to first attack, number of attacks, asthma control score and quality of life. Adherence to ICS treatment is objectively measured by an electronic logging device. Participants are invited to participate in a “phenotyping” assessment where skin prick reactivity and bronchodilator response are determined and a saliva sample is collected for DNA extraction. Qualitative interviews will be held with participants and research nurses. A health economic evaluation will take place.

Discussion

This study will evaluate whether FENO can provide an objective index to guide and stratify asthma treatment in children.

Trial registration

ISRCTN, ISRCTN67875351. Registered on 12 April 2017. Prospectively registered.
Malaria outbreak investigation in Tanquae Abergelle district, Tigray region of Ethiopia: a case–control study
Authors: Tesfay Kissanet , Assefa Belete , Addisu Alefech
Published: October 2019

Objective

We investigated this outbreak to describe the magnitude and associated risk factors due to the malaria outbreak in Tanquae Abergelle district, Tigray, Ethiopia, in 2017.

Result

Case fatality rate of this study was zero. Among the 62 cases and 124 controls, the presence of mosquito breeding sites [OR = 6.56 CI (2.09–20.58) P value = 0.001], sleeping outside a home [OR = 5.06 CI (1.75–14.61) P-value = 0.003] and having unscreened window [OR = 14.89 CI (1.87–118.25) P-value = 0.011] were associated with illness in multivariate analysis.
A new PacBio genome sequence of an Australian Pyrenophora tritici-repentis race 1 isolate
Authors: Moolhuijzen Paula , See Pao Theen , Moffat Caroline S.
Published: October 2019

Objectives

The necrotrophic fungal pathogen Pyrenophora tritici-repentis (Ptr) is the causal agent of tan spot a major disease of wheat. We have generated a new genome resource for an Australian Ptr race 1 isolate V1 to support comparative ‘omics analyses. In particular, the V1 PacBio Biosciences long-read sequence assembly was generated to confirm the stability of large-scale genome rearrangements of the Australian race 1 isolate M4 when compared to the North American race 1 isolate Pt-1C-BFP.

Results

Over 1.3 million reads were sequenced by PacBio Sequel small-molecule real-time sequencing (SRMT) cell to yield 11.4 Gb for the genome assembly of V1 (285X coverage), with median and maximum read lengths of 8959 bp and 72,292 bp respectively. The V1 genome was assembled into 33 contiguous sequences with a of total length 40.4 Mb and GC content of 50.44%. A total of 14,050 protein coding genes were predicted and annotated for V1. Of these 11,519 genes were orthologous to both Pt-1C-BFP and M4. Whole genome alignment of the Australian long-read assemblies (V1 to M4) confirmed previously identified large-scale genome rearrangements between M4 and Pt-1C-BFP and presented small scale variations, which included a sequence break within a race-specific region for ToxA, a well-known necrotrophic effector gene.
Treatment of bipolar depression with supraphysiologic doses of levothyroxine: a randomized, placebo-controlled study of comorbid anxiety symptoms
Authors: Pilhatsch Maximilian , J Stamm Thomas , Stahl Petra , Lewitzka Ute , Berghöfer Anne , Sauer Cathrin , Gitlin Michael , Frye Mark A. , Whybrow Peter C. , Bauer Michael
Published: October 2019

Background

Symptoms of anxiety co-occur in a variety of disorders including in depressive episodes of bipolar disorder and in patients with thyrotoxicosis. Treatment of refractory bipolar disorder with supraphysiologic doses of levothyroxine (L-T4) has been shown to improve the phenotypic expression of the disorder and is associated with an increase of circulating thyroid hormones. However, it might be associated with somatic and mental adverse effects. Here we report the investigation of the influence of treatment with supraphysiologic doses of L-T4 on symptoms of anxiety in patients with refractory bipolar depression.

Methods

Post-hoc analysis from a 6-week, multi-center, randomized, double-blind, placebo-controlled study of the effects of supraphysiologic L-T4 treatment on anxiety symptoms in bipolar depression. Anxiety symptoms were measured weekly with the Hamilton anxiety/somatization factor (HASF) score of the Hamilton Depression Rating Scale (HAMD) and the State- and Trait Anxiety Inventory (STAI).

Results

Treatment of both groups was associated with a significant reduction in anxiety symptoms (p < 0.001) with no statistical difference between groups (LT-4: from 5.9 (SD = 2.0) at baseline to 3.7 (SD = 2.4) at study end; placebo: from 6.1 (SD = 2.4) at baseline to 4.4 (SD = 2.8) at study end; p = 0.717). Severity of anxiety at baseline did not show a statistically significant correlation to the antidepressive effect of treatment with supraphysiologic doses of L-T4 (p = 0.811). Gender did not show an influence on the reduction of anxiety symptoms (females: from 5.6 (SD = 1.7) at baseline to 3.5 (SD = 2.4) at study end; males: from 6.1 (SD = 2.3) at baseline to 4.0 (SD = 2.4) at study end; p = 0.877).

Conclusions

This study failed to detect a difference in change of anxiety between bipolar depressed patients treated with supraphysiologic doses of L-T4 or placebo. Comorbid anxiety symptoms should not be considered a limitation for the administration of supraphysiologic doses of L-T4 refractory bipolar depressed patients.

Trial registration ClinicalTrials, ClinicalTrials.gov identifier: NCT01528839. Registered 2 June 2012—Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT01528839
Ammonium alum in alum-treated wooden artefacts: discovery, origins and consequences
Authors: McQueen Caitlin M. A. , Łucejko Jeannette J. , Flåte Ingrid M. T. , Modugno Francesca , Braovac Susan
Published: October 2019

Alum-treatment was extensively applied to archaeological wood from the Oseberg collection in the early 1900s, and was a common conservation method at the time involving impregnating objects with hot concentrated solutions of potassium alum (KAl(SO4)2⋅12H2O). This now obsolete consolidation method has led to dramatic long-term consequences, heavily affecting the state of preservation of the historical wooden artefacts, and dedicated chemical characterisation campaigns have been undertaken to better understand the degradation processes and aid development of re-treatment strategies. Analyses with Fourier transform infrared spectroscopy (FTIR), elemental microanalysis, and ion chromatography (IC) was performed, suggesting the presence of ammonium alum (NH4Al(SO4)2·12H2O) in many alum-treated wood samples, though no record exists of use of ammonium compounds during treatment of the artefacts. C/N rations of 1.70–68.8 in wood samples, and ammonium alum contents between 8 and 84% of the alum component and 23–168 mmol/100 g of total sample suggested that objects were actually treated with various mixes of potassium and ammonium alum. The two alums have similar properties, and in model studies of their behaviour under the conditions of alum-treatment appeared to form similarly acidic solutions, thus the different alum mixtures probably did not significantly influence object treatment. Nor have we observed other indications of unusual degradation pathways related specifically to the presence of ammonium alum. Nonetheless, investigations into potential re-treatment of the archaeological objects must be adjusted accordingly.
Egg recognition in Cinereous Tits (Parus cinereus): eggshell spots matter
Authors: Liu Jianping , Yang Canchao , Yu Jiangping , Wang Haitao , Liang Wei
Published: October 2019

Background

Brood parasitic birds such as cuckoos (Cuculusspp.) can reduce their host’s reproductive success. Such selection pressure on the hosts has driven the evolution of defense behaviors such as egg rejection against cuckoo parasitism. Studies have shown that Cinereous Tits (Parus cinereus) in China have a good ability for recognizing foreign eggs. However, it is unclear whether egg spots play a role in egg recognition. The aims of our study were to investigate the egg recognition ability of two Cinereous Tit populations in China and to explore the role of spots in egg recognition.

Methods

To test the effect of eggshell spots on egg recognition, pure white eggs of the White-rumped Munia (Lonchura striata) and eggs of White-rumped Munia painted with red brown spots were used to simulate experimental parasitism.

Results

Egg experiments showed that Cinereous Tits rejected 51.5% of pure white eggs of the White-rumped Munia, but only 14.3% of spotted eggs of the White-rumped Munia. There was a significant difference in egg recognition and rejection rate between the two egg types.

Conclusions

We conclude that eggshell spots on Cinereous Tit eggs had a signaling function and may be essential to tits for recognizing and rejecting parasitic eggs.
Quality improvement in mental health services
Authors: Boland Billy
Published: October 2019

Quality improvement (QI) approaches are becoming increasingly important in the delivery of mental healthcare internationally. They were originally developed in the manufacturing industry, but the principle of having a systematic approach to improvement has spread to many other industries, not least to healthcare. Quality improvement approaches in healthcare were pioneered in the USA at organisations such as Virginia Mason and the Institute for Healthcare Improvement. In recent years, they have become firmly established in mental health services in the UK's National Health Service (NHS). There are a number of different approaches to quality improvement, but two leading models have taken root: ‘lean thinking’ (also known as ‘lean methodology’ or simply ‘lean’), which arose out of Virginia Mason, and the ‘Model for Improvement’, which came out of the Institute of Healthcare Improvement. This article describes these two quality improvement approaches, critiques their philosophy and explores how they can apply in the provision of mental healthcare, particularly with reference to the use of data, evidence and metrics.
Knowledge and Use of Cervical Cancer Screening Among University Female Students at Kilimanjaro, Tanzania
Authors: Joel Hollo , Mduma Dorcas , Mawolle Jackline , Rogathi Jane
Published: October 2019

PURPOSE

Cervical cancer is a major public and global health problem. According to the WHO, it is the fourth leading cancer among women worldwide, with most women being from low- or middle-income countries. It is the leading cause of cancer-related morbidity and mortality among women of reproductive age in Tanzania, where approximately 4,216 women die as a result of the disease annually. Women with HIV/AIDS, multiple sexual partners, history of human papillomavirus infections, contraceptive use, and early onset of sexual activity have increased risk of the disease, including among university students. Poor knowledge and limited screening programs are major contributors. This study was aimed at assessing the level of knowledge and use of cervical cancer screening among university female students in Moshi municipality.

METHODS

A cross-sectional study was conducted from June to July 2018 involving undergraduate female students age 18 years and older at three different universities in the Moshi municipality. A total of 322 participants were identified using multistage sampling; data were collected through a self-administered semistructured questionnaire and analyzed using SPSS version 20.

RESULTS

Ninety-two participants (28.6%) had good knowledge, 104 (32.3%) had satisfactory knowledge, and 126 (39.1%) had poor knowledge. About 299 (92.9%) had heard about cervical cancer. The most frequent sources of information were the media (168 [52.2%]); family, neighbors, and friends (106 [32.9%]), health workers (102 [31.7%]); and teachers (75 [23.3%]). Few reported other sources of information. Only 31 women (9.6%) had been screened for cervical cancer. The reasons given for not attending cervical cancer screening were “I have just not decided” (114 [30.4%]), “I am healthy” (81 [21.6%]), “I’m not informed” (49 [13.0%]), and “It may be painful” (42 [11.2%]); 89 women (23.7%) reported other reasons.

CONCLUSION

Lack of proper knowledge about cervical cancer contributes to low-screening use. Promotion to increase awareness about cervical cancer screening through radio, television, social media, and clubs would be of great importance. Although a lot has been done by the government and other stakeholders regarding screening, the campaigns should focus not only on women but also on university students specifically, who are more likely to have multiple sexual partners and to have engaged in sexual activity at younger than 18 years.
Breast Cancer and the Environment: A Pilot Study of Nigerian Women
Authors: Li Suellen , Huo Dezheng , Ojengbede Oladosu , Olopade Olufunmilayo
Published: October 2019

PURPOSE

Breast cancer remains the leading cause of cancer in women throughout the world, and its incidence has been increasing markedly in Africa. Women of African ancestry not only develop breast cancer at earlier ages but also have more aggressive breast cancers, with higher prevalence of TP53 mutations and triple-negative breast cancer. Although environment-induced TP53 mutagenesis has been well described in liver and lung cancers, few studies have explored its role in breast cancer. In addition, most prior studies were done in white populations and lacked generalizability to women of other ancestries. This pilot study aimed to investigate the association between environmental risk factors and somatic mutation status. A sub-aim was to evaluate the feasibility and effectiveness of a questionnaire-based method for gathering environmental exposure data.

METHODS

Twenty-nine patients with breast cancer and 33 patients from Ibadan, Nigeria, who had participated in the Nigerian Breast Cancer Study, were contacted to complete an environmental risks questionnaire that assessed household air pollution, diet, occupational hazards, and sleep habits. The questionnaire was translated into Yoruba and conducted with local interpreters, who obtained informed consent from all participants. Both the institutional review boards at the University of Chicago and the University of Ibadan approved the project.

RESULTS

The results showed that cases were more likely to report living close to a major road, waste incinerator, or factory ( P = .046). There were also significant differences in occupation ( P = .000), with cases more likely to report professional occupations. They were also more likely to report occupational exposures to mineral dust, exhaust, chemicals, and endocrine disruptors; night shift work; and preference for well-done meat, although these did not reach statistical significance.

CONCLUSION

This study suggests that examining exposures to environmental risk factors may be a promising avenue for future breast cancer research. The study design limited the validity of comparing exposures between cases and controls but demonstrated that a questionnaire-based method is both feasible and effective at gathering environmental exposure data. Future studies would benefit from more formal interviewer training to improve the quality of the data collection, more culturally relevant questions to assess stressful life events, and a prospective design to reduce recall bias and loss to follow-up.
Evaluating the Effect of Medicaid Expansion on Black/White Breast Cancer Mortality Disparities: A Difference-in-Difference Analysis
Authors: Semprini Jason , Olopade Olufunmilayo I.
Published: October 2019

PURPOSE

This analysis used a difference-in-difference (DID) fixed effects regression model to evaluate the impact of Medicaid Expansion on the disparity between black and white breast cancer mortality rates. Medicaid Expansion was designed to increase access to health care. Evidence is mixed, but theory and empirical data suggest that lower cost of care, through greater access to insurance, increases health care utilization and possibly improves the health of poor and sick populations. The goal of Medicaid Expansion was to improve equity. However, this major health policy has yet to be thoroughly investigated for its effect on health disparities. Many widely accepted methods exist to evaluate variations in health policy, but few studies have used such quasi-experimental designs to explore health disparities. The current study is motivated by one of today’s most stark inequalities: the disparity in breast cancer mortality rates between black and white women. To test the impact Medicaid Expansion had on the black/white breast cancer mortality ratio, a DID analysis calculated the policy’s average treatment effect (ATE).

METHODS

State-level breast cancer mortality data were obtained from the Centers for Disease Control and Prevention. Each state’s Medicaid Expansion status was provided by a Kaiser Family Foundation white paper. Two tests were conducted: one compared all expanding states with all nonexpanding states, and the other compared all expanding states with nonexpanding states that voted to expand (but did not by 2014). Fixed-effects and random-effects regression models were constructed for each specific age group. A Hausman test was calculated to determine which model was most appropriate. The DID regression models considered the year 2014 a wash-out period and compared 2012 and 2013 (pretreatment) to 2015 and 2016 (post-treatment). A graph was presented to test the necessary parallel trend assumption for expanding and nonexpanding states. DID estimators (average treatment effect) and respective P values were reported for each age group. Non–Medicaid-eligible age groups were included as a pseudo-control.

RESULTS

Medicaid Expansion did not lower the disparity in breast cancer mortality. Converse to expectations, the black/white mortality ratio increased in states expanding Medicaid for all Medicaid-eligible age groups, with significant effects in younger age groups ( P = .01 to .15).

CONCLUSION

Investigators should use proven quasi-experimental methods to analyze the effect of policy variation on health disparities. Policy makers must consider institutional factors that may limit minority groups from benefiting from macrochanges in health policy. These results suggest that states cannot solely rely on access to insurance to alleviate disparities in cancer or other chronic conditions. More exploration into the impacts of low-quality health systems remain warranted.
Using Technology to Improve Quality of Cancer Care in Resource-Limited Settings
Authors: Silas O.A. , Achenbach C.J. , Hou L. , Murphy R.L.
Published: October 2019

PURPOSE

To highlight the importance of adapting affordable, holistic point-of-care technology (POCT) and data management software to improve quality of cancer care in resource-limited settings. Cancer is the second leading cause of death globally and was responsible for an estimated 9.6 million deaths in 2018, with low- and middle-income countries accounting for as much as 70% of these deaths.

METHODS

In 2004, the WHO outlined a set of criteria, called the ASSURED guidelines, to promote affordable, sensitive, specific, user-friendly, rapid, robust, equipment-free, and deliverable to end-user POCT. Although advances in POC cancer technology are relatively underexploited, early successes show that the field has significant potential to contribute to improving cancer detection, diagnosis, and treatment in low- and middle-income countries.

RESULTS

The current global disparity in cancer care can be addressed through mobilization of the research community to improve POCT, funding unique POCT concepts adapted for resource-limited settings, and training of scientists and engineers in designing robust data management software, such as the research electronic data capture for cancer research.

CONCLUSION

Improving cancer care holistically requires use of POCT with designs adapted to resource-limited settings and leveraging software with robust features for cancer research.
Meat ants cut more trail shortcuts when facing long detours
Authors: Oberhauser F. B. , Middleton E. J. T. , Latty T. , Czaczkes T. J.
Published: October 2019

Engineered paths increase efficiency and safety but also incur construction and maintenance costs, leading to a trade-off between investment and gain. Such a trade-off is faced by Australian meat ants, which create and maintain vegetation-free trails between nests and food sources, and thus their trails are expected to be constructed selectively. To test this, we placed an artificial obstacle consisting of 300 paper grass blades between a sucrose feeder and the colony, flanked by walls of either 10 or 80cm length. To exploit the feeder, ants could detour around the walls or take a direct route by traversing through the obstacle. We found that, when confronted with a long alternative detour, 76% of colonies removed more grass blades and ants were also 60% more likely to traverse the obstacle instead of detouring, with clearing activity favouring higher ant flow or vice versa. An analysis of cut patterns revealed that ants did not cut randomly, but instead concentrated on creating a trail to the food source. Meat ants were thus able to collectively deploy their trail clearing efforts in a directed manner when detour costs were high, and rapidly established cleared trails to the food source by focussing on completing a central, vertically aligned trail which was then followed by the ants.