bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of the Spatial Heterogeneity of Breast Cancers: Associations Between Computed Tomography and Immunohistochemistry
Authors: Woolf David K , Li Sonia P , Detre Simone , Liu Alison , Gogbashian Andrew , Simcock Ian C , Stirling James , Kosmin Michael , Cook Gary J , Siddique Muhammad , Dowsett Mitch , Makris Andreas , Goh Vicky
Published: June 2019

Background:

Tumour heterogeneity is considered an important mechanism of treatment failure. Imaging-based assessment of tumour heterogeneity is showing promise but the relationship between these mathematically derived measures and accepted ‘gold standards’ of tumour biology such as immunohistochemical measures is not established.

Methods:

A total of 20 women with primary breast cancer underwent a research dynamic contrast-enhanced computed tomography prior to treatment with data being available for 15 of these. Texture analysis was performed of the primary tumours to extract 13 locoregional and global parameters. Immunohistochemical analysis associations were assessed by the Spearman rank correlation.

Results:

Hypoxia-inducible factor-1α was correlated with first-order kurtosis ( r = −0.533, P = .041) and higher order neighbourhood grey-tone difference matrix coarseness ( r = 0.54, P = .038). Vascular maturity-related smooth muscle actin was correlated with higher order grey-level run-length long-run emphasis ( r = −0.52, P = .047), fractal dimension ( r = 0.613, P = .015), and lacunarity ( r = −0.634, P = .011). Micro-vessel density, reflecting angiogenesis, was also associated with lacunarity ( r = 0.547, P = .035).

Conclusions:

The associations suggest a biological basis for these image-based heterogeneity features and support the use of imaging, already part of standard care, for assessing intratumoural heterogeneity.
Across five levels: The evidence of impact model
Authors: Harper Lesley M. , Maden Michelle , Dickson Rumona
Published: June 2019

This article describes The Evidence of Impact Model that was recently developed to support the analysis of short- to medium-term impact arising from Participatory Action Research and Developmental Evaluation approaches that were used within the Evidence for Change initiative. Evidence for Change was a team capacity building initiative that supported rapid, bottom-up, evidence informed change in health and social care environments. To explain the need for The Evidence of Impact Model and outline how it was developed, a variety of similar models are explored and the challenges of capturing impact arising from Evidence for Change are discussed. The resulting new model based on the existing concept of micro, meso and macro levels of impact is outlined in detail with supporting qualitative evidence. The authors conclude that The Evidence of Impact Model provides an effective lens for exploring impact at a variety of levels within an emerging and complex environment.
Bayesian prediction of bridge extreme stresses based on DLTM and monitoring coupled data
Authors: Liu Yuefei , Fan Xueping
Published: June 2019

For predicting dynamic coupled extreme stresses of bridges with monitoring coupled data, this article considers monitoring extreme stress data as a time series, and takes into account its coupling generated by the fusion of non-stationarity and randomness. First, the local polynomial theory is introduced, and the local polynomial order of monitoring coupled extreme stress data is estimated with time-series analysis method. Second, based on time-series analysis results, dynamic linear trend models (DLTM) and the corresponding Bayesian probability recursive processes are given to predict dynamic coupled extreme stresses. Finally, through the illustration of monitoring coupled extreme stress data from an actual bridge, the proposed method, which is compared with the traditional Bayesian dynamic linear models, is proved to be more effective for predicting dynamic coupled extreme stresses of bridges.
‘I mean, why wouldn’t men be involved?’ The life histories of six male practitioners working within early childhood education and care in England
Authors: Jones Charlotte Estella , Aubrey Carol
Published: June 2019

Many surveys and interviews have elicited male practitioners’ views about gender balance in the early childhood education and care workforce, and few have explored in depth the context to such work choices, whether economic, cultural, social or personal. A life history approach was employed to provide a retrospective account by six early childhood education and care professionals of their lives and some of the influences on these. They varied in job role, in organisation that employed them and in their ages ranging from 20 to 60 years. Being at different stages of their life course, some had lived through considerable societal change in education, job choice, attitudes and values. The life history approach also offered a means to explore broader questions about their professional development, links between life and work that rose above the individual voice to represent the profession that participants had chosen.
How Parental Attachment Influences College Students’ Social Domains
Authors: Wright Stephen L. , Lyon Allegra R.
Published: June 2019

We investigated how parental continued attachment was related to college students’ social provision areas during the early phases of college to better understand student persistence factors. Using a sample of undergraduate students ( N = 419), we applied structural equation modeling and found that mother and father continued attachment affects the social provisions of students in different ways. Mother attachment was related to nurturance and emotional connection, whereas father attachment was related to worth, guidance, alliance, and emotional connection. These relational and social provision areas may serve as influence factors related to college student persistence. Limitations and implications for student persistence, development, researchers, and educators are discussed.
Estradiol and NADPH oxidase crosstalk regulates responses to high fat feeding in female mice
Authors: Ronis Martin J , Blackburn Michael L , Shankar Kartik , Ferguson Matthew , Cleves Mario A , Badger Thomas M
Published: June 2019

We previously demonstrated protection against high fat-induced obesity in female but not male p47phox−/− mice lacking NADPH oxidase NOX1/2 activity. To test the role of estradiol (E2)-NOX crosstalk in development of this sexually dimorphic phenotype, we fed diets containing 42% fat/0.5% cholesterol to intact and ovariectomized wild type female C57BL/6 mice and female p47phox−/− mice and to ovariectomized mice where the diet was supplemented with an 1 mg/kg 17β estradiol (E2) for 12 weeks from PND28. Weight gain, gonadal fat pad weight, serum leptin and adiponectin, and adipose tissue inflammation were greater in intact wild type vs. p47 mice ( P < 0.05). Genotype effects on body weight/fat mass were abolished after ovariectomized and restored in OVX + E2 mice ( P < 0.05). The mRNA of downstream PPARγ targets CD36, lipoprotein lipase, and leptin was higher in intact wild type vs. p47phox−/− mice mice ( P < 0.05). Likewise, intact high fat-fed wild type mice had higher expression of the cytokine Mcp1; the pyroptosis marker Nirp3 and matrix remodeling and fibrosis markers Mmp2, Col1A1, and Col6a3 mRNAs ( P < 0.05). These genotype effects were reversed and restored by ovariectomized and OVX + E2, respectively ( P < 0.05). These data suggest that triglyceride accumulation in adipose tissue and development of adipose tissue injury in response to feeding diets high in fat and cholesterol is regulated by the balance between NOX-dependent reactive oxygen species signaling and E2-signaling during development. Loss of estrogens post menopause may increase the risk of obesity and metabolic syndrome as the result disinhibition of reactive oxygen species signaling.

Impact statement

Estrogens are known to regulate body composition. In addition, reactive oxygen species (ROS) produced by the action of NADPH oxidase (NOX) enzymes have been linked to obesity development. We examined development of obesity and adipose tissue injury in response to feeding “Western” diets high in fat and cholesterol in intact, ovariectomized (OVX), and estrogen-replaced (OVX + E2) wild type and p47phox−/− female mice where NOX2 activity is inhibited. Weight gain, gonadal fat pad weight, and adipose tissue inflammation were greater in intact WT vs. p47phox−/− mice. Genotype effects on body weight/fat mass were abolished after OVX and restored in OVX + E2 mice. These data indicate adipose tissue responses to feeding the “Western” diet is regulated by negative cross-talk between NOX-dependent ROS signaling and E2-signaling during development. Loss of estrogens post menopause may increase the risk of obesity and metabolic syndrome as the result disinhibition of ROS signaling.
Downregulation of WW domain-containing oxidoreductase leads to tamoxifen-resistance by the inactivation of Hippo signaling
Authors: Li Juan , Feng Xuefei , Li Canyu , Liu Jie , Li Pingping , Wang Ruiqi , Chen He , Liu Peijun
Published: June 2019

Acquired tamoxifen-resistance is an important cause of death in patients with hormone-dependent breast tumors. Therefore, understanding the molecular mechanisms underlying the development of tamoxifen-resistance is critical for successful endocrine therapy. This study aimed to define the role of WW domain-containing oxidoreductase (WWOX) in acquired tamoxifen-resistance. Our results show that low WWOX expression was significantly related to tamoxifen-resistance. Moreover, WWOX-knockdown increased resistance to tamoxifen, while WWOX overexpression decreased the resistance. Furthermore, WWOX silencing decreased Yes-associated protein (YAP) phosphorylation and increased YAP nuclear translocation. Finally, YAP silencing decreased tamoxifen-resistance in WWOX-knockdown cells. Our findings demonstrate that WWOX downregulation can lead to the development of tamoxifen-resistance by inactivating Hippo signaling. Thus, WWOX might be a valuable target and prognostic marker for tamoxifen-resistance.

Impact statement

Understanding the molecular pathways leading to the development of tamoxifen-resistance is an important research focus as acquired tamoxifen-resistance is the main cause of death in patients with benign primary prognosis. Although WW domain-containing oxidoreductase (WWOX) has been related to breast tumorigenesis, its role in acquired tamoxifen-resistance has not yet been demonstrated. Our findings show that WWOX might be a valuable therapeutic target and prognostic marker for tamoxifen-resistance.
Investigating the effects of wicking and antibacterial finishing treatments on some comfort characteristics of Meryl skinlife for seamless activewear/sportswear
Authors: Gocek İkilem , Duru Sena Cimilli
Published: June 2019

Antibacterial efficacy and wearing comfort have recently become particular concerns in the activewear and sportswear market for consumers. Meryl skinlife, which is an antibacterial polyamide fiber due to the silver particles in its content, has been increasingly used in the textile industry, and it is mostly preferred for seamless garments that are especially used for activewear and sportswear. From this point of view, in this study fabrics made of Meryl skinlife fibers were investigated in terms of some water-related comfort properties by comparing their performance with that of their counterparts made of conventional polyamide fibers. Also, the effects of Lycra incorporation into the fabric structure and fiber type as well as antibacterial finishing treatments were examined on the wicking ability and comfort performance of the fabric samples. The vertical wicking capacity, transfer wicking, drying rate, and water vapor permeability tests were conducted on the fabric samples and the results of these tests were statistically analyzed using the Minitab and SPSS statistical package programs. The results showed that Lycra incorporation into the fabric structure was found to be the dominant factor for all of the investigated water-related comfort tests except for transfer wicking, while application of the finishing treatments was found to be the dominant factor for all of the investigated comfort-related tests. However, the fiber type was found influential on none of the comfort-related tests conducted in this study. Finally, the hybrid analytic hierarchy process-TOPSIS method was used to determine the best fabric alternative for activewear and sportswear, and it was found that SLN fabrics were the best choice.
Three-dimensional-printed patient-specific Kirschner-wire guide for percutaneous fixation of undisplaced scaphoid fractures: a cadaveric study
Authors: Salabi Vincent , Rigoulot Guillaume , Sautet Alain , Cambon-Binder Adeline
Published: June 2019

Undisplaced scaphoid waist fractures can be managed by percutaneous fixation. The purpose of this study is to compare percutaneous fixation using a three-dimensional (3-D)-printed guide with the conventional method in a cadaveric study. Twelve wrists were divided into two groups: standard fluroscopic technique group, and a patient-specific 3-D-printed guide group. In the patient-specific group, using high resolution CT scans, we manufactured a mould-guide including a wire guide sleeve aligned with the planned ideal path, and 3-D printed it. On postoperative CT scans we measured the angular deviation of the screw axis from the ideal axis, and compared the two groups. The angular deviation was significantly lower in the patient-specific guide group. We concluded that a 3-D-printed guide for scaphoid percutaneous fixation allows a more accurate placement of the screw than a fluoroscopy guide in our cadaveric model.
Pacinian neuromas and neurofibromas of the hands and fingers: a systematic review
Authors: Fassola Isabella , Wenzke Lena , Ertel Wolfgang , Krasnici Senat
Published: June 2019

Tumours involving Pacinian corpuscles are rare. The literature identifies two main pathological disorders: the Pacinian corpuscle neuroma or hyperplasia and the Pacinian corpuscle neurofibroma. Published data are confusing and at times conflicting. This systematic review summarizes the available data in order to support clinicians in the differential diagnosis with other tumours responsible for unclear symptoms in the hands and fingers. We identified 67 pertinent articles. Although some similarities have been described, the two tumours have relevant differences, specifically when comparing age of the patient, location, symptoms, characteristic of a mass, and aetiology. All these factors should be taken into account in order to improve diagnostic accuracy. Despite the low incidence of unsuccessful surgeries, extraordinary measures are occasionally necessary to achieve complete resolution of symptoms.
The effect of the bend radius on the impulse transfer characteristics of V-hulls: Numerical simulations
Authors: Langdon Genevieve Sarah , Shekhar Vinay
Published: June 2019

A study was performed to investigate the effects of geometry on impulse transfer to V-plates subjected to localised air-blast loading. The V-plates were designed to be 1:8 scale compared to the full-scale V-hulls used in landmine-protected vehicles. Simulations were performed using LS-DYNA and validated using results from blast experiments on scaled rigid V-plated structures of varying internal angle. The validated numerical models were then used to ascertain the influence of including the clamp, varying the stand-off distance, internal angle and V-tip radius on impulse transfer. The simulations showed that, in general, the impulse increased as V-tip radius increased. For the 90° and 120° V-plates, the impulse transferred was observed to plateau for bend radii greater than 160 mm. The increase in impulse was attributed to changes in the spatial and temporal load distribution due to the higher V-tip radius. There was no significant variation in the pressure distributions for larger bend radii (above 160 mm). For both the 90° and 120° V-plates, a dip in impulse was observed when the V-tip radii was between 0 and 20 mm. This was caused by reduced peak pressures and an increase in gas flow. Fixing the clearance height and increasing the V-tip radius (and therefore the stand-off distance) had no discernible effect on impulse transfer. However, it was shown to increase the arrival time and load duration, while decreasing the peak total force.
The effect of lithium chloride on the motor function of spinal cord injury–controlled rat and the relevant mechanism
Authors: Chen Gang , Liang Yimin , Chen Fanghu , Wang Haifeng , Zhu Guoming
Published: June 2019

The objective of this study is to discuss the effect and mechanism of lithium chloride on the rehabilitation of locomotion post spinal cord injury (SCI) by observing the effect of lithium chloride on the expression of the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) pathway. In total, 36 Sprague-Dawley (SD) rats were randomly divided into the sham operation group (n = 12), model group (n = 12), and lithium chloride group (n = 12). The sham operation group underwent laminectomy, while for the model group and the lithium chloride group with the NYU spinal cord impactor the SCI model was established. Basso, Beattie, and Bresnahan (BBB) score was used to evaluate locomotion after administration for 1, 3, 5, and 7 days, and the tissues were gathered for Nissl staining, transmission electron microscopy, immunofluorescence, and Western blot. With a statistical difference ( P < 0.05) on the 3rd day and significant difference ( P < 0.01) on the 5th day post administration, a higher BBB score was observed in the lithium chloride group indicating that lithium chloride improved the locomotion function after SCI. A better structure and morphology of neuron were observed by Nissl staining in the lithium chloride group. Lithium chloride promoted BDNF secretion from neurons in the spinal cord anterior horn with a significant difference compared to the model group ( P < 0.01). Compared with the model group, lithium chloride significantly promoted the expression of BDNF protein and phosphorylated TrkB protein ( P < 0.05), but no difference in the expression of TrkB was detected. Lithium chloride can alleviate the locomotion function after SCI with a mechanism that it can promote BDNF secretion from neurons in the spinal cord anterior horn and phosphorylation of TrkB to upregulate the BDNF/TrkB pathway supporting survival of neurons and regeneration and remyelination of axons.
The Effects of Various Hemostatic Agents on Shear-bond Strength in Primary Teeth: An In Vitro Study
Authors: Delikan Ebru , Cantekin Kenan
Published: June 2019

Aims and objectives:

The aim of this study was to determine the effects of chitosan, Ankaferd Blood Stopper®(ABS, Ankaferd Health Products Ltd, Turkey), and ferric sulfate (FS) on the shear-bond strength of the self-etch adhesive to primary tooth dentin.

Materials and methods:

The occlusal surfaces of 80 extracted human primary teeth (stored in a 0.5% chloramine-T solution at 4oC) were ground flat, exposing the dentin. The teeth were divided into 4 groups: chitosan, ABS, FS, and control. Hemostatic agents were applied to the teeth, and then they were rinsed with distilled water and air dried. In the control group, the teeth were only rinsed with distilled water and slightly air dried. A self-etch adhesive was applied, and the composite cylinder was created on all the samples. Shear-bond strength was tested with a universal testing machine. Failure mode analysis was performed using scanning electron microscopy.

Results:

The study revealed no statistically significant difference between the hemostatic agent and control groups in terms of bond strength ( P >.05). The highest bond strength was observed in the chitosan group. In this group, a statistically significant difference between chitosan and ABS was observed ( P <.05). The adhesive failure was the predominant failure mode in all the groups.

Conclusions:

These findings suggest that chitosan, ABS, and FS have no adverse effects on the bonding of the self-etch adhesive to primary teeth dentin.
Knowledge and Attitude Toward Electric Toothbrush Use Among Dental Professionals in Saudi Arabia
Authors: Al-Kattan Reem , Al-Shibani Nouf
Published: June 2019

Background:

Proper knowledge and awareness regarding electric toothbrushes may decrease the incidence of caries and indirectly reduce the burden of oral disease on the developing economy by preventing plaque-related disease on a population level.

Aims and objectives:

The aim of this study was to assess the knowledge and attitude toward electric toothbrush use among dentist in Saudi Arabia.

Materials and methods:

An analytical cross-sectional study was conducted among 417 dentists in Saudi Arabia. For this study, an interview-type questionnaire comprising 14 questions was designed. These questions were asked from different dentists randomly through a telephonic survey. The first part of the questionnaire was related to the basic demographic details of the dentists, that is, gender, age, type of practice, dental education, specialty, and experience, whereas the second part of the questionnaire was designed to extract the experience, attitude, and opinion of the dentists regarding electric toothbrushes. The data were compiled and analyzed using Statistical Product and Service Solutions, version 20 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were employed to calculate means and percentages for demographic data.

Results:

Among the dental participants, 171 (41.0%) were general practitioners, 163 (39.0%) were specialist, 23 (5.6%) were postgraduate students, and 60 (14.4%) were graduate dentists. A total of 271 (65%) respondents believed better patient compliance to be the main benefit of the electric toothbrush, whereas 325 (77.9%) respondents believed that poor patient compliance was the reason for patient’s poor plaque control. Similarly, 319 (76.5%) dentists endorsed patients with manual dexterity issues. Those dentists primarily recommended electric toothbrushes to patients with medical problems.

Conclusions:

Knowledge of dentists in Saudi Arabia is adequate regarding electric toothbrushes; efforts should be made to improve knowledge and awareness on the use of powered toothbrushes at the patients’ level.
Circulating monocytes and tumor‐associated macrophages express recombined immunoglobulins in glioblastoma patients
Authors: Busch Svenja , Talamini Marina , Brenner Steffen , Abdulazim Amr , Hänggi Daniel , Neumaier Michael , Seiz‐Rosenhagen Marcel , Fuchs Tina
Published: June 2019

Background

Glioblastoma is the most common and malignant brain tumor in adults. Glioblastoma is usually fatal 12–15 months after diagnosis and the current possibilities in therapy are mostly only palliative. Therefore, new forms of diagnosis and therapy are urgently needed. Since tumor‐associated macrophages are key players in tumor progression and survival there is large potential in investigating their immunological characteristics in glioblastoma patients. Recent evidence shows the expression of variable immunoglobulins and TCRαβ in subpopulations of monocytes, in vitro polarized macrophages and macrophages in the tumor microenvironment. We set out to investigate the immunoglobulin sequences of circulating monocytes and tumor‐associated macrophages from glioblastoma patients to evaluate their potential as novel diagnostic or therapeutic targets.

Results

We routinely find consistent expression of immunoglobulins in tumor‐associated macrophages (TAM) and circulating monocytes from all glioblastoma patients analyzed in this study. However, the immunoglobulin repertoires of circulating monocytes and TAM are generally more restricted compared to B cells. Furthermore, the immunoglobulin expression in the macrophage populations negatively correlates with the tumor volume. Interestingly, the comparison of somatic mutations, V‐chain usage, CDR3‐length and the distribution of used heavy chain genes on the locus of chromosome 14 of the immunoglobulins from myeloid to B cells revealed virtually no differences.

Conclusions

The investigation of the immunoglobulin repertoires from TAM and circulating monocytes in glioblastoma‐patients revealed a negative correlation to the tumor volume, which could not be detected in the immunoglobulin repertoires of the patients’ B lymphocytes. Furthermore, the immunoglobulin repertoires of monocytes were more diverse than the repertoires of the macrophages in the tumor microenvironment from the same patients suggesting a tumor‐specific immune response which could be advantageous for the use as diagnostic or therapeutic target.
Evolutionary biology: an essential basic science for the training of the next generation of psychiatrists
Authors: Abed Riadh , Ayton Agnes , St John-Smith Paul , Swanepoel Annie , Tracy Derek K.
Published: June 2019

Evolutionary science can serve as the high-level organising principle for understanding psychiatry. Evolutionary concepts generate new models and ideas for future psychiatric study, research, policy and therapy. The authors accordingly make the case for the inclusion of evolutionary biology in the postgraduate education of psychiatric trainees.
Transition between child and adult services for young people with attention-deficit hyperactivity disorder (ADHD): findings from a British national surveillance study
Authors: Eke Helen , Ford Tamsin , Newlove-Delgado Tamsin , Price Anna , Young Susan , Ani Cornelius , Sayal Kapil , Lynn Richard M. , Paul Moli , Janssens Astrid
Published: June 2019

Background

Optimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.

Aims

To estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.

Method

Surveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.

Results

Questionnaire response was 79% at baseline and 82% at follow-up. For those aged 17–19, incident rate (range adjusted for non-response) of transition need was 202–511 per 100 000 people aged 17–19 per year, with successful transition of 38–96 per 100 000 people aged 17–19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.

Conclusions

As inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.
Disturbances in Insulin–Glucose Metabolism in Patients With Advanced Renal Disease With and Without Diabetes
Authors: Rahhal Marie-Noel , Gharaibeh Naser Eddin , Rahimi Leili , Ismail-Beigi Faramarz
Published: June 2019

Context

Use of insulin in patients with diabetes and advanced chronic kidney disease (CKD; stages 4 to 5) is challenging and shows great variability among individuals. We explored the mechanisms underlying this variability.

Evidence Acquisition

PubMed was searched for articles in English from 1960 to 2018 for advanced CKD and diabetes, glucose and insulin metabolism, insulin clearance, secretion and resistance, plasma insulin concentration, glycemic control, hypoglycemia, insulin dosage, and continuous glucose monitoring (CGM) in CKD.

Evidence Synthesis

The evidence shows that in most patients the daily dose of insulin needs to be significantly reduced with a high degree of variability; in some the dose remains unchanged, and rarely it is increased. The premise that the marked reduction in insulin requirement is essentially attributable to decreased insulin clearance by kidneys leading to prolongation of its plasma half-life, elevated blood insulin concentration, and hypoglycemia is not entirely correct. Other factors including decreases in food intake, insulin secretion, insulin clearance by peripheral tissues, and renal gluconeogenesis play important roles. There is also heightened resistance to insulin due to metabolic acidosis, uremic toxins, inflammatory state, and vitamin D deficiency. Importantly, the magnitude of changes in each of these factors varies between individuals with the same degree of CKD.

Conclusions

In the presence of diabetes with advanced CKD, the insulin regimen should be individualized based on knowledge of the daily glucose patterns. The use of CGM is promising for safer glycemic control in patients with advanced CKD and diabetes and helps prevent extremes of hypoglycemia and hyperglycemia.
Total Syntheses of the Non-Peptide Bradykinin B1 Receptor Antagonist Velutinol A and Its Analogs,seco-Pregnanes with a Cage-Like Moiety
Authors: Tamiya Minoru , Isaka Nobuhisa , Kitazawa Takaaki , Hasegawa Atsushi , Ishizawa Kazuya , Ikeda Mayu , Kawada Saki , Ishiguro Masaji
Published: June 2019

We describe here the syntheses of velutinol A (1) and the structurally similar compounds 2–4 sharing a highly oxygenated seco-pregnane cage-like structure. The synthesis of velutinol A (1, 15,16-seco-pregnane) features the highly regioselective construction of Δ14 silyl enol ether from 15-keto-21,22-diol, followed by stereoselective introduction of a sterically hindered β-hydroxy group at the C14 position by Rubottom oxidation. Prolonged reaction time and the use of an excess amount of mCPBA at this step allowed double Rubottom oxidation, enabling us to introduce the requisite hydroxy groups at the C14 and C16 positions in one pot. Subsequent oxidative cleavage of the C15–16 bond, deprotection, and intramolecular acetalization allowed the concise total synthesis of velutinol A (1). Utilization of α,α-dihydroxyketone, the double Rubottom oxidation product, for formation of the ether F-ring by 5-exo-cyclization, and subsequent C14–21 oxidative cleavage, effectively achieved the synthesis of pentalinonside-aglycon (2). Construction of the 14,15-seco-structures of two other analogs, argeloside aglycon (3) and illustrol (4), was achieved by Baeyer–Villiger oxidation of 15(21)-keto derivatives. Introduction of the 20-oxo group potentially embedded in argeloside aglycon was accomplished by Wacker oxidation of Δ20, which was constructed by Grieco–Nishizawa syn-β-elimination of the C21-primary alcohol obtained by reduction of the Baeyer–Villiger product. Intramolecular double acetalization of the 15,16-dihydroxy-14,20-oxo derivative to form the cage-like structure of the DEF-rings required a moderately weak acid. This step was the key to accessing argeloside aglycon (3), as otherwise the easily aromatized β,γ-dihydroxyketone moiety was transformed to furan. Sharpless asymmetric dihydroxylation of Δ20 to set the C20 stereocenter, followed by intramolecular double acetalization, achieved the stereoselective synthesis of illustrol With all synthesized compounds, structural requirements of steroidal bradykinine B1 receptor antagonist would be revealed.
African Pharmacogenomics Consortium: Consolidating pharmacogenomics knowledge, capacity development and translation in Africa
Authors: Dandara Collet , Masimirembwa Collen , Haffani Yosr Z. , Ogutu Bernhards , Mabuka Jenniffer , Aklillu Eleni , Bolaji Oluseye ,   H3Africa
Published: June 2019

The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent.  Africa, especially south of the Sahara, is beset with a huge burden of infectious diseases with much co-morbidity whose multiplicity and intersection are major challenges in achieving the sustainable development goals (SDG), SDG3, on health and wellness. The profile of drugs commonly used in African populations lead to a different spectrum of adverse drug reactions (ADRs) when compared to other parts of the world. Coupled with the genetic diversity among Africans, the APC is established to promote pharmacogenomics research and its clinical implementation for safe and effective use of medicine in the continent.  Variation in the way patients respond to treatment is mainly due to differences in activity of enzymes and transporters involved in pathways associated with each drug’s disposition.  Knowledge of pharmacogenomics, therefore, helps in identifying genetic variants in these proteins and their functional effects. Africa needs to consolidate its pharmacogenomics expertise and technological platforms to bring pharmacogenomics to use.
The Value of Commitments When Selling to Strategic Consumers: A Supply Chain Perspective
Authors: Kabul Mustafa O. , Parlaktürk Ali K.
Published: June 2019

We consider a decentralized supply chain consisting of a retailer and a supplier that serves forward-looking consumers in two periods. In each period, the supplier and the retailer dynamically set the wholesale and retail price to maximize their own profits. The consumers are heterogeneous in their evaluations of the product and are strategic in deciding whether and when to buy the product, choosing the option that maximizes their utility, including waiting for a price markdown. We derive the equilibrium and study the value of price and quantity commitments from both the retailer’s and the supplier’s perspectives. We find that, although a centralized system always benefits from making price and quantity commitments, this is not true for a firm in a decentralized supply chain due to how the other firm responds to these commitments. We show that the retailer suffers from making a price or quantity commitment and that, similarly, the supplier does not benefit from making a price commitment. In these cases, commitments can harm not only the firm itself but also profitability of the other firm in the supply chain, thereby disadvantaging the entire supply chain. This happens because such commitments aggravate double-marginalization inefficiency in the supply chain. Furthermore, we show that eliminating this inefficiency through a coordinating contract (e.g., a two-part tariff or quantity discount) makes commitments beneficial.

This paper was accepted by Martin Lariviere, operations management.
a guide to Level 3 apprenticeship standard: Standard issue
Authors: Crown Hannah
Published: June 2019

The sector's first-ever Early Years Educator apprenticeship standard, at Level 3, has finally landed. Here's a handy guide from Hannah Crown
Kidnapping for fun and profit? Voluntary abduction, extreme consumption and self-making in a risk society
Authors: Yar Majid , Tzanelli Rodanthi
Published: June 2019

This article explores the emerging phenomenon of ‘staged kidnapping’, a consumer-oriented experience in which individuals voluntarily subject themselves to abduction and associated experiences of detention, deprivation, interrogation and degradation. We explore the staging, presentation and consumption of voluntary abduction through an analysis of the online marketing and reporting of the phenomenon, to consider the ways new consumerist trends alter traditional notions of hospitality. We analyse the phenomenon’s emergence within the twin theoretical frames of Beck’s ‘risk society’ thesis and Lyng’s account of ‘voluntary risk-taking’ as a form of ‘edgework’. We argue that the framing and appeal of such experiences can be fruitfully located as an element in the reflexive production of the post-traditional self, a process that requires subjects to confront and manage (materially or symbolically) the conditions of risk and uncertainty that characterize contemporary inhospitable lifeworlds.
Lebanese food, ‘Lebaneseness’ and the Lebanese diaspora in London
Authors: Abdallah Ali , Fletcher Thomas , Hannam Kevin
Published: June 2019

Lebanese food, as a cultural tradition, and in the context of Lebanese migration, mobility and diasporic identity, is the focus of this article. We use ethnographic methods in the form of participant observation, focus groups and semi-structured interviews with restaurant owners, workers and members of the Lebanese diaspora to critically examine the connections between diasporic identity and Lebanese food in London. The analysis revealed that Lebanese migrants living in London are highly affected and influenced by their homeland and its traditions. Analysis also revealed how the Lebanese hospitality industry has grown and adapted, becoming embedded, hybridized and contested by members of the Lebanese diaspora. We argue that this contestation revolves around a mobile sense of place and belonging.
The ‘McAutocrat of the breakfast-table’: Highland hospitality in nineteenth-century travel writing
Authors: James K. J.
Published: June 2019

The concept of the tourism imaginary can be employed to illuminate representational histories of the inn and the innkeeper in the nineteenth-century Scottish Highlands. In evaluations of Scottish hospitality, the innkeeper’s relationship to modern tourism culture was appraised in tandem with the wider role of the inn and its local social, cultural and commercial functions. Some commentators critiqued Highland tourism practices as inhospitable, often through caricatures of the miserly innkeeper. Other writers treated Highland inns as indices of local economic prosperity, and the innkeeper as either an upholder of local morality or a victim of economic structures and even climatic conditions. As the tourism sector expanded, a variety of texts positioned inns and innkeepers at the heart of debates over the relationship between Highland culture and practices of commercial hospitality.
Webs of significance: Articulating latent value structures in a rural cafe organized as a worker cooperative
Authors: Powell Lawrence , Wang Pola , O’Neill Linda , Dentice Glenn , Neill Lindsay
Published: June 2019

This research seeks to clarify the staff value commitments that underlie hospitality ventures that choose to organize themselves as worker cooperatives. Although some studies have focused on organizational and economic aspects of such participatory, cooperative businesses, less is known about the staff values. This study examines the shared ‘social values’ and ‘business culture’ at Riverside Café, a small business established to bring additional revenues in support of Riverside Community – a 78-year-old rural pacifist community located near Motueka, New Zealand. To elaborate the values and associated business culture, and how the two interact in everyday life at Riverside Café, semi-structured qualitative interviews were conducted with staff. Based on the transcribed recordings, dominant themes and subthemes were identified and classified. Salient clusters of ‘values’ emerging from the interviews were Harmony (peaceful living, tolerance, compassion, non-harming, balance), Social Justice (equality, freedom, sharing, creative craftsmanship), Interconnectedness (cooperation, community, right livelihood, sustainability), Trust (social bonds, reliability) and Post-materialism (‘people over things’, unselfishness, spirituality). Salient clusters of ‘business culture’ norms identified were Non-hierarchical Management and Service, and Commercial Imperatives. The discovered value categories highlight both the advantages and limitations of operating cafes as worker cooperatives.
Assessment and final reports in foreign language lessons
Authors: Çubukçu Feryal
Published: June 2019

Psycholinguists are interested in how words are stored in human memory. The question as to whether words are stored as single root words or whether they are stored along with the affixes still remains a controversial issue. Aitchison (1987) believes that each word has a separate entry. Mackay (1978) and Taft (1981) hold that words are made of constituent morphemes. When we listen, we decompose the morphemes and when we speak, we combine them to make multimorphemic words. The decomposition view claims that only the root is stored in memory. To test this claim, a group of 50 intermediate level students at the preparatory department of a state university situated on the western coast of Turkey were selected. They were taught 10 pseudo root nouns and verbs and 10 psuedo complex nouns and verbs. To see how the morphological complexity affected lexical access and which type of words were better remembered, they were tested on these words. Then the same group was given 10 root and 10 complex words in their mother tongue and their answer times were compared. Students recalled the root words more easily and accurately.The results shed light on the validity of the decomposition theory, showcasing we remember the words in roots better.
GLOBAL EVOLUTION AND PALEOGEOGRAPHIC DISTRIBUTION OF
MID - CRETACEOUS ORBITOLINIDS
Authors: Boudagher-Fadel Marcelle , Price G. David
Published: June 2019

Members of the Larger Benthic Foraminiferal (LBF) family Orbitolinidae occured from the Cretaceous to the Paleogene, however, they were most diverse during the mid-Cretaceous, and dominated the agglutinated LBF assemblages described from limestones of that period. Various orbitolinid species have been used to zone and date lithologies formed in the shallow, warm waters of the Aptian to the Early Cenomanian, and many, sometimes inaccurate, generic and sub-generic nomenclatures have been proposed to differentiate the often subtle morphological changes that orbitolinids exhibit over time. Until now, it has not been possible to develop an effective global overview of their evolution and environmental development because descriptions of specimens from Asia have been relatively rare. Following our recent study of over 1800 orbitolinid-rich thin sections of material from 13 outcrops of the Langshan Limestone, from the Southern Tibetan Plateau, and from the Barito Basin, South Kalimantan, Indonesia, it has been possible to compare the stratigraphic ranges of these orbitolinids with previously described Tethyan and American forms, based on the use of a planktonic zonal (PZ) scheme, itself tied to the most recent chronostratigraphic scale. This has allowed the reconstruction of the phylogenetic and paleogeographic evolution of the orbitolinids from their Valanginian origin in the Tethys. Although Tethys remained the paleogeographic focus for the orbitolinids, it is inferred here for the first time that a bi-directional paleogeographic migration of some orbitolinid genera occurred from Tethys to the Americas and also to the Western Pacific region. Our observations and dating confirm that global marine regressions in the Aptian were coincident with, and may well have facilitated, these orbitolinid transoceanic migrations. However, migration stopped after rising sea-level in the Early Albian appears to have again isolated these provinces from each other. Tectonic forces associated with the subduction of the Farallon Plate and further sea-level raises led to the opening of the Western Interior Seaway in the North America, which correlates with, and may have been the cause of, the Middle Albian (top of PZ Albian 2) extinction of the American orbitolinids. The extinction of the orbitolinids revealed that the Western Pacific province was split into two sub-provinces, with extinction occurring at the end of the Early Albian (top of PZ Albian 1) in the Northwest Pacific sub-province, and at the end of the Albian (top of PZ Albian 4) in the sub-province that is today South East Asia (on the margins and west of the Wallace Line). The final virtual extinction of the orbitolinids occurred at the end of the Cenomanian in the Tethyan province, which coincides with, and may have been caused by, global anoxic oceanic events that correlate with a near-peak Mesozoic eustatic sea-level high-stand that led to the overall global collapse of the paleotropical reef ecosystem at that time.
Real time mitochondrial dimension measurements
Authors: M. Leichner Joseph , Konyukhov Evgene , Kamoun David , Yaniv Yael
Published: June 2019

Mitochondrial volume is correlated with cell function and internal cell processes. Changes in mitochondrial volume were associated with advanced states of cardiac disease. Thus, measurements of mitochondrial dimension deformations are important to the understanding of cell function and its deterioration. Existing methods either allow measurements of the volume of isolated mitochondria, which are an inferior model to that of isolated cells, or they allow short time measurements that are toxic to the cells. Recent studies have discovered that mitochondrial deformation along a given cell axis can be measured by using the Fourier transformation on the variation in transmitted light intensity induced by the periodic lattice of myofilaments alternating with mitochondrial rows. However, this method was used only offline and in a line scan mode, making it impossible to measure both axes. We designed an open source program in LabVIEW to take advantage of the transmitted light diffraction technique and quantify mitochondrial two dimension (2D) deformation in cardiomyocytes, in situ in real time for long periods (more than several seconds). We validated the program on synthetic and on experimental images from rabbit and rat ventricular myocytes. The program can analyze offline and real time simultaneous 2D mitochondrial deformation dynamics as well as also sarcomere length dynamics. Moreover, the program can accurately analyze images acquired from different cameras. Quantification of mitochondrial 2D deformations is a powerful tool for exploring cell biophysics and bioenergetics mechanisms and will lay the foundation for a future clinical tool for quantifying mitochondrial volume changes associated with different cardiac diseases.
A step-by-step beginner’s protocol for whole genome sequencing of human bacterial pathogens
Authors: S. Gautam Sanjay , KC Rajendra , WC Leong Kelvin , Aogáin Micheál Mac , F. O’Toole Ronan
Published: June 2019

Bacterial whole genome sequencing (WGS) is becoming a widely-used technique in research, clinical diagnostic, and public health laboratories. It enables high resolution characterization of bacterial pathogens in terms of properties that include antibiotic resistance, molecular epidemiology, and virulence. The introduction of next-generation sequencing instrumentation has made WGS attainable in terms of costs. However, the lack of a beginner’s protocol for WGS still represents a barrier to its adoption in some settings. Here, we present detailed step-by-step methods for obtaining WGS data from a range of different bacteria (Gram-positive, Gram-negative, and acid-fast) using the Illumina platform. Modifications have been performed with respect to DNA extraction and library normalization to maximize the output from the laboratory consumables invested. The protocol represents a simplified and reproducible method for producing high quality sequencing data. The key advantages of this protocol include: simplicity of the protocol for users with no prior genome sequencing experience and reproducibility of the protocol across a wide range of bacteria.